NEW INDICATION OF CARDIOVASCULAR DRUGS FOR PREPARATION OF CANCER INHIBITION PHARMACEUTICAL COMPOSITION

Info

Publication number: 20170304388
Type: Application
Filed: Oct 23, 2015
Publication Date: Oct 26, 2017
Applicant: LAUNX BIOMEDICAL CO., LTD. (Kaohsiung)
Inventors: Chiu-Hung Chen (Kaohsiung), Show-Mei Chuang (Taichung), Nai-Wan Hsiao (Taichung), Ruei-Yue Liang (Taichung), Xiao-Tong Tan (Taichung)
Application Number: 15/521,536

Abstract

A method for treating a cancer includes administering to a subject in need thereof a pharmaceutical composition containing a therapeutically effective amount of a cardiovascular drug or a pharmaceutical acceptable salt thereof. The cardiovascular drug is selected from the group consisting of peripheral vasodilator reaming enhancer, angiotensin converting agent inhibitor, hypotension and shock therapeutic agent, diuretic, antiarrhythmic agent, antiarralciton drug, antihypertensive agent, anticoagulant thrombolytic agent, cardiac tonic, and intravenous (hemorrhoids) therapeutic agent. The cancer is selected from the group consisting of lung cancer, intestinal cancer, colorectal cancer, prostate cancer, liver cancer, bladder cancer, cervical cancer, breast cancer, and blood cancer.

Description

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a National Phase Application filed under 35 U.S.C. 371 as a national stage of PCT/CN2015/092768 filed Oct. 23, 2015, an application claiming the benefit under 35 USC 119(e) to the following U.S. Provisional Applications No. 62/068,298 filed Oct. 24, 2014, the content of each of which is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention provides new clinical indication of cardiovascular drugs, which were approved by FDA. Particularly, the present invention demonstrates that the cardiovascular drugs can effectively inhibit a variety of cancers.

BACKGROUND OF THE INVENTION

Cancer is the most popular disease cause of death in the world. The cancer patients are gradually increase yearly, therefore the treatment method of the cancer has become an important issue. The medical treatments of cancer can be classified as surgical treatment, radiation therapy, chemotherapy and target therapy.

Generally, the cancer drug, whether chemotherapy drug or target therapy drug, is inhibit the cancer cells' duplication and split to prevent the tumor growth and metastasis. In clinical treatment options, the combination of chemotherapies and several targeted therapies were selected; try to eliminate cancer cells more effectively, by means of different mechanisms. Furthermore, if the cancer patients happen the drug resistance, that would reduce the effectiveness of the drugs and result in the medical treatment failure.

On the other side, treatment of cardiovascular disease aims to prevent or delay the progression of the disease. Also, it aims to reduce the risk of developing cardiovascular diseases. For example, some cardiovascular drugs can treat high blood pressure, and other cardiovascular drugs can promote blood flow in patients with heart failure.

Based on the many years' experience of inventors, the human cancer cells and normal cells often have different characteristics, the differences in patterns or mechanism variation might be seen as a foreign invader. The different cancel cells are located in different locations and the statuses of variations are related to the located environment. Thus, the inventors are the first person to propose the use of antibiotic drugs to inhibit the cancer cell growth.

In contrast, these cardiovascular drugs have been used for decades and are recognized by FDA long time ago. These cardiovascular drugs already have been researched and analyzed to know the mechanism on human body. Therefore, the groundbreaking new application would be time-saving and cost effective if these drugs applied in treating cancer. Besides, the treatment effect would be improved if these drugs are used to combine with other treating method.

Otherwise, the manufacturing of the drug is also a big problem. When the drug starting the clinical trials, there are lots of problems need to overcome, such as drug safety, patient selection, trial dose and other issues. Even the drug has approved by the FDA and sales on the market, there still possibly face the situation of the poor drug response in patients. Furthermore, if the cancer patients happen the drug resistance, that would reduce the effectiveness of the drugs and result in the medical treatment failure. Therefore, the new drug development is very difficult.

SUMMARY OF THE INVENTION

To solve the above problems, the present invention provides a usage of existing cardiovascular drugs, which have passed clinical trials.

The experiment results showed that the cardiovascular drugs had no toxicity or only little toxicity to normal cells. However, there are more studies need to be test to know that whether the cardiovascular drugs have selection between normal cells and cancer cells. Besides, not all the cardiovascular drugs could inhibit the growth of cancer cells under same condition, there are still lots of problems need to be overcame.

Term Definition

The cardiovascular drugs can be classified to ten categories based on the features, includes: peripheral vasodilator reaming enhancer, angiotensin converting agent inhibitor, hypotension and shock therapeutic agent, diuretic, antiarrhythmic agent, antiarralciton drug, antihypertensive agent, anticoagulant and thrombolytic agent, cardiac tonic, intravenous (hemorrhoids) therapeutic agent.

(1) Peripheral vasodilator reaming enhancer, which can directly or indirectly effect on peripheral blood vessels to increase blood flow, includes: Cilnidipine, Minoxidil, Prazosin HCl, Sildenafil citrate, Tadalafil (Cialis), Nicorandil (Ikorel), Lacidipine (Lacipil, Motens), Benidipine hydrochloride, Cilazapril monohydrate (Inhibace), Fosinopril sodium (Monopril), Almotriptan malate (Axert), Milrinone (Primacor), Avanafil, Lomerizine HCl, Histamine Phosphate, Chromocarb and Pinacidil.

(2) Angiotensin converting agent inhibitor, which is used to inhibit ACE activity and reduce the production of vasopressin II, so as to reduce the bradykinin hydrolysis, lead to vasodilatation, blood volume, and decrease blood pressure, includes: Benazepril hydrochloride, Losartan potassium, Perindopril Erbumine (Aceon), Irbesartan (Avapro), Candesartan (Atacand), Olmesartan medoxomil (Benicar), Enalaprilat dehydrate, Telmisartan (Micardis), Ramipril (Altace), Valsartan (Diovan), Enalapril maleate (Vasotec), Candesartan cilexetil (Atacand), Conivaptan HCl (Vaprisol), Azilsartan Medoxomil (TAK-491) and Eprosartan Mesylate.

(3) Hypotension and shock therapeutic agent, which includes: L-Adrenaline (Epinephrine), DL-Adrenaline and Methoxamine HCl.

(4) Diuretic, which is used to increase the generation of urine and increase the excretion of human body water, includes: Bumetanide, Furosemide (Lasix), Metolazone(Zaroxolyn), Silodosin (Rapaflo), Chlorothiazide, Trichlormethiazide (Achletin), Torsemide (Demadex), Hydrochlorothiazide, Indapamide (Lozol), Dichlorphenamide (Diclofenamide), Amiloride hydrochloride dehydrate, Solifenacin succinate, Methyclothiazide, Benzthiazide, Meticrane, Bendroflumethiazide and Potassium Canrenoate.

(5) Antiarrhythmic agent, which is used to inhibit abnormal heartbeat rhythm (arrhythmia), such as atrial fibrillation, atrial flutter, and ventricular tachycardia (ventricular tachycardia) and ventricular fibrillation, includes: Adenosine (Adenocard), Dofetilide (Tikosyn), Amiodarone HCl, Ibutilide fumarate, Propafenone (Rytmonorm) and Disopyramide Phosphate.

(6) Antiarralciton drug, which is used to treat ischemic heart disease symptoms, includes Dexrazoxane Hydrochloride, Ranolazine dihydrochloride, Nisoldipine (Sular), Ranolazine (Ranexa), Acadesine, Nifedipine (Adalat), Amlodipine besylate (Norvasc), Diltiazem HCl (Tiazac), Ticagrelor and Oxprenolol HCl

(7) Antihypertensive agent is a medicament for hypertension treatment, which is used to prevent high blood pressure complications, such as stroke and myocardial infarction, includes: Bisoprolol, Doxazosin mesylate, Alfuzosin hydrochloride (Uroxatral), Nebivolol (Bystolic), Reserpine, Methyldopa (Aldomet), Eplerenon, Nimodipine (Nimotop), Betaxolol hydrochloride (Betoptic), Carvedilol, Metoprolol tartrate, Felodipine (Plendil), Amlodipine (Norvasc), Phentolamine mesilate, Imidapril (Tanatril) HCl, Aliskiren hemifumarate, Sodium Nitroprusside, Propranolol HCl, Levobetaxolol HCl, Esmolol HCl, (R)-(+)-Atenolol, Guanethidine Sulfate and Lofexidine HCl.

(8) Anticoagulant, thrombolytic agent is the flag used to prevent blood coagulation (coagulation). Those substances exist in leeches and blood-sucking insects. Anticoagulants can treat thrombotic diseases, include: Prasugrel (Effient), Cilostazol, Nafamostat mesylate, Clopidogrel (Plavix), Apixaban, Aminocaproic acid (Amicar), Dipyridamole (Persantine), Phenindione (Rectadione), Ticlopidine HCl, Ozagrel HCl, Argatroban, Bexarotene, Gabexate mesylate and Ozagrel and Anisindione.

(9) Cardiac tonic includes: Pimobendan (Vetmedin), Ampiroxicam, Digoxigenin and Pindolol.

(10) Intravenous (hemorrhoids) therapeutic agent includes: Edaravone (MCI-186), Daidzein, Ginkgolide A and Bisacodyl.

In one of the embodiments, the cancer is selected from lung cancer, intestinal cancer, colorectal cancer, prostate cancer, liver cancer, bladder cancer, cervical cancer, breast cancer and blood cancer.

In one of the embodiment of the present invention, wherein the effect concentration of the drug in the present invention is 20 mg/kg/day˜500 mg/kg/day.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the analysis of cardiovascular drugs for cancer cells inhibition.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a usage of cardiovascular drugs for cancer inhibition pharmaceutical composition preparation, which feature is the pharmaceutical composition composed by an effective dosage of cardiovascular drug and a pharmaceutical acceptable salt.

The cardiovascular drug of the present invention includes: Lenalidomide Valproic acid sodium salt (Sodium valproate), Decitabine, Bisoprolol, Dexrazoxane Hydrochloride, Prasugrel (Effient), Benazepril hydrochloride, Bumetanide, Cilnidipine, Cilostazol, Doxazosin mesylate, Edaravone (MCI-186), Losartan potassium, Minoxidil, Nafamostat mesylate, Bimatoprost, Alfuzosin hydrochloride (Uroxatral), Clopidogrel (Plavix), Prazosin HCl, Ranolazine dihydrochloride, Sildenafil citrate, Perindopril Erbumine (Aceon), Irbesartan (Avapro), Tadalafil (Cialis), Nebivolol (Bystolic), Pimobendan (Vetmedin), Candesartan (Atacand), Apixaban, Reserpine, Furosemide (Lasix), Olmesartan medoxomil (Benicar), Pyridostigmine Bromide (Mestinon), Metolazone (Zaroxolyn), Silodosin (Rapaflo), Chlorothiazide, Methyldopa (Aldomet), Adenosine (Adenocard), Ezetimibe (Zetia), Enalaprilat dehydrate, Dofetilide (Tikosyn), Trichlormethiazide (Achletin), Aminocaproic acid (Amicar), Busulfan (Myleran, Busulfex), Torsemide (Demadex), Eplerenone, Hydrochlorothiazide, Gemfibrozil (Lopid), Indapamide (Lozol), Telmisartan (Micardis), Nimodipine (Nimotop), Nisoldipine (Sular), Pitavastatin calcium (Livalo), Simvastatin (Zocor), Ramipril (Altace), Fenofibrate (Tricor, Trilipix), Ranolazine (Ranexa), Acadesine, Acipimox, Nifedipine (Adalat), Amlodipine besylate (Norvasc), Clofibrate (Atromid-S), Betaxolol hydrochloride (Betoptic), Carvedilol, Daidzein, toprolol tartrate, Diltiazem HCl (Tiazac), Tranexamic acid (Transamin), Felodipine (Plendil), Valsartan (Diovan), Dipyridamole (Persantine), Amlodipine (Norvasc), Fluvastatin sodium (Lescol), Phenindione (Rectadione), Enalapril maleate (Vasotec), Nicorandil (Ikorel), Amiodarone HCl, Ticlopidine HCl, Lacidipine (Lacipil, Motens), Suplatast tosylate, Benidipine hydrochloride, Ginkgolide A, Candesartan cilexetil (Atacand), Phentolamine mesilate, Nimesulide, Cytidine, Bromhexine HCl, Tiopronin (Thiola), Ozagrel HCl, Argatroban, Mitiglinide calcium, Rosiglitazone HCl, Atorvastatin calcium (Lipitor), Famotidine (Pepcid), Cleviprex (Clevidipine), Cilazapril monohydrate (Inhibace), Adiphenine HCl, Rivastigmine tartrate (Exelon), Detomidine HCl, Fosinopril sodium (Monopril), Almotriptan malate (Axert), Bexarotene, Gabexate mesylate, Rasagiline mesylate, Imidapril (Tanatril) HCl, Conivaptan HCl (Vaprisol), Ibutilide fumarate, Probucol, Arbidol HCl, S-(+)-Rolipram, Tebipenem pivoxil (L-084), Dichlorphenamide (Diclofenamide), Aliskiren hemifumarate, DL-Carnitine hydrochloride, D-Mannitol (Osmitrol), L-carnitine (Levocarnitine), Amantadine hydrochloride (Symmetrel), Clozapine (Clozaril), Milrinone (Primacor), Mitoxantrone Hydrochloride, Novobiocin sodium (Albamycin), Ozagrel, Pancuronium (Pavulon), Propafenone (Rytmonorm), Quinine hydrochloride dehydrate, Spectinomycin hydrochloride, Xylazine HCl, L-Adrenaline (Epinephrine), DL-Adrenaline, Trospium chloride (Sanctura), Amiloride hydrochloride dehydrate, Cloxacillin sodium (Cloxacap), Zidovudine (Retrovir), Thiamphenicol (Thiophenicol), Oseltamivir phosphate (Tamiflu), Lonidamine, Peramivir Trihydrate, Carfilzomib (PR-171), Pazopanib, Fosaprepitant dimeglumine, Otilonium Bromide, Solifenacin succinate, Besifloxacin HCl (Besivance), Azilsartan Medoxomil (TAK-491), Creatinine, Adrenalone HCl, Ampiroxicam, Desloratadine, Avanafil, Bisacodyl, Methyclothiazide, Sodium Nitroprusside, Vitamin D3 (Cholecalciferol), Deferiprone, Propranolol HCl, Mefenamic acid, Ticagrelor, sulfacetamide sodium, Lomerizine HCl, Levobetaxolol HCl, Dexlansoprazole, Esmolol HCl, Eprosartan Mesylate, Histamine Phosphate, Sevelamer HCl, Deoxyarbutin, Clorprenaline HCL, Ethamsylate, Chromocarb, Mevastatin, Mexiletine HCl, Phenazopyridine HCl, (R)-(+)-Atenolol, Anisindione, Benzthiazide, Disopyramide Phosphate, Guanethidine Sulfate, Isoetharine Mesylate, Methoxamine HCl, Meticrane, Oxprenolol HCl, Pinacidil, Bendroflumethiazide, Potassium Canrenoate, Digoxigenin, Lofexidine HCl and Pindolol.

Cell Culture

Subculture the different types of cancer cells. The cancer cells includes lung cancer, gastric cancer, hepatic cancer, colon cancer, skin cancer, cervical cancer, prostate cancer, bladder cancer, breast cancer, leukemia, pancreatic cancer, ovarian cancer, tongue cancer, osteosarcoma, and renal cancer. Cancer cell lines were cultured in different culture medium according to different characteristics (as shown in Table 1). The cell numbers were counted and reseed as 2×10⁶in cell culture plate/flask. Then, the culture medium for culturing the cell lines was added to a volume of 10 ml, and the cells were cultured for 2-3 days. Then, the cells were suspended for loading into 96-well plates. The cell number was 3000 cells and the volume of the culture medium was 100 ul each well.

TABLE 1 Cancer cell lines and the culture medium tumor Cell line Culture medium Lung cancer H1650 (Lung Adenocarcinoma) RPMI A549 (Lung Adenocarcinoma) DMEM Stomach cancer AGS (Gastric Adenocarcinoma) RPMI MKN-45 (Gastric Adenocarcinoma) RPMI Liver cancer HepG2 (Hepatocellular Carcinoma) DMEM Intestinal HCT116 (Colorectal Carcinoma) DMEM cancer LoVo (Colorectal Adenocarcinoma) DMEM Skin cancer A375 (Amelanotic Melanoma) DMEM Cervical cancer HeLa (Cervix Adenocarcinoma) DMEM Pr^ostate cancer PC3 (Prostate Adenocarcinoma) DMEM Bladder cancer TSGH-8301 (Urinary Bladder Carcinoma) RPMI Breast cancer MCF7 (Mammary Gland, Adenocarcinoma) DMEM Leukemia HL-60 (Acute Promyelocytic Leukemia) RPMI

Cell Viability Analysis

Removing the original culture medium from 96-well plate. Then add 100 μl of commercially drug at a concentration of 10 μM per well. After 72 hours, add the diluted WST-1 reagent to the well with 100 μl/well, and the diluted WST-1 reagent was acquired from the dilution of 9:1 medium and WST-1 stock reagent. Finally, the total volume of each well are 200 μl/well. Culture the 96-well plate at 37° C. for 30 to 90 minutes. Detecting and calculating the survival rate of each cancer cells with an ELISA reader at OD450 nm. The lower viability of cancer cells represents better inhibition effect via the drugs. Otherwise, the higher viability of cancer cells represents worse inhibition effect via the drugs.

Growth Inhibitory Effects on Cancer Cell Lines by Various Cardiovascular Drugs in the Present Invention

For cell viability analysis, the cardiovascular drugs include peripheral vasodilator reaming enhancer, angiotensin converting agent inhibitor, hypotension and shock therapeutic agent, diuretic, antiarrhythmic agent, antiarralciton drug, antihypertensive agent, anticoagulant thrombolytic agent, cardiac tonic, intravenous (hemorrhoids) therapeutic agent, are used to test the inhibition effect of cancer cell.

The test result showed that lots of cardiovascular drugs had no effect on cancer cell lines growth inhibition (Table 2).

TABLE 2 The cardiovascular drugs which do not have significant inhibitory effect to cancer cells Numbers of inhibitory cardiovascular drugs effect on cancer cell line Bisoprolol 0 Benazepril hydrochloride 0 Bumetanide 0 Furosemide (Lasix) 0 Trichlormethiazide (Achletin) 0 Aminocaproic acid (Amicar) 0 Indapamide (Lozol) 0 Simvastatin (Zocor) 0 Ramipril (Altace) 0 Fenofibrate (Tricor, Trilipix) 0 Acadesine 0 Acipimox 0 Ticlopidine HCl 0 Adiphenine HCl 0 Rivastigmine tartrate (Exelon) 0 Detomidine HCl 0 Gabexate mesylate 0 Rasagiline mesylate 0 S-(+)-Rolipram 0 Tebipenem pivoxil (L-084) 0 Aliskiren hemifumarate 0 Milrinone (Primacor) 0 Novobiocin sodium 0 Ozagrel 0 Pancuronium (Pavulon) 0 Propafenone (Rytmonorm) 0 Xylazine HCl 0 L-Adrenaline (Epinephrine) 0 Lonidamine 0 Bisacodyl 0 Sodium Nitroprusside 0 Mefenamic acid 0 Ticagrelor 0 sulfacetamide sodium 0 Levobetaxolol HCl 0 Dexlansoprazole 0 Chromocarb 0 Guanethidine Sulfate 0 Isoetharine Mesylate 0

Besides, the inhibition effects of different cardiovascular drugs on different cancer cells were different (shown as FIG. 1). According to the experiment, the Lenalidomide, Valproic acid sodium salt (Sodium valproate), Decitabine, Bisoprolol, Dexrazoxane Hydrochloride, Prasugrel (Effient), Benazepril hydrochloride, Bumetanide, Cilnidipine, Cilostazol, Doxazosin mesylate, Edaravone (MCI-186), Losartan potassium, Minoxidil, Nafamostat mesylate, Bimatoprost, Alfuzosin hydrochloride (Uroxatral), Clopidogrel (Plavix), Prazosin HCl, Ranolazine dihydrochloride, Sildenafil citrate, Perindopril Erbumine (Aceon), Irbesartan (Avapro), Tadalafil (Cialis), Nebivolol (Bystolic), Pimobendan (Vetmedin), Candesartan (Atacand), Apixaban, Reserpine, Furosemide (Lasix), Olmesartan medoxomil (Benicar), Pyridostigmine Bromide (Mestinon), Metolazone (Zaroxolyn), Silodosin (Rapaflo), Chlorothiazide, Methyldopa (Aldomet), Adenosine (Adenocard), Ezetimibe (Zetia), Enalaprilat dehydrate, Dofetilide (Tikosyn), Trichlormethiazide (Achletin), Aminocaproic acid (Amicar), Busulfan (Myleran, Busulfex), Torsemide (Demadex), Eplerenone, Hydrochlorothiazide, Gemfibrozil (Lopid), Indapamide (Lozol), Telmisartan (Micardis), Nimodipine (Nimotop), Nisoldipine (Sular), Pitavastatin calcium (Livalo), Simvastatin (Zocor), Ramipril (Altace), Fenofibrate (Tricor, Trilipix), Ranolazine (Ranexa), Acadesine, Acipimox, Nifedipine (Adalat), Amlodipine besylate (Norvasc), Clofibrate (Atromid-S), Betaxolol hydrochloride (Betoptic), Carvedilol, Daidzein, toprolol tartrate, Diltiazem HCl (Tiazac), Tranexamic acid (Transamin), Felodipine (Plendil), Valsartan (Diovan), Dipyridamole (Persantine), Amlodipine (Norvasc), Fluvastatin sodium (Lescol), Phenindione (Rectadione), Enalapril maleate (Vasotec), Nicorandil (Ikorel), Amiodarone HCl, Ticlopidine HCl, Lacidipine (Lacipil, Motens), Suplatast tosylate, Benidipine hydrochloride, Ginkgolide A, Candesartan cilexetil (Atacand), Phentolamine mesilate, Nimesulide, Cytidine, Bromhexine HCl, Tiopronin (Thiola), Ozagrel HCl, Argatroban, Mitiglinide calcium, Rosiglitazone HCl, Atorvastatin calcium (Lipitor), Famotidine (Pepcid), Cleviprex (Clevidipine), Cilazapril monohydrate (Inhibace). Adiphenine HCl, Rivastigmine tartrate (Exelon), Detomidine HCl, Fosinopril sodium (Monopril), Almotriptan malate (Axert), Bexarotene, Gabexate mesylate, Rasagiline mesylate, Imidapril (Tanatril) HCl, Conivaptan HCl (Vaprisol), Ibutilide fumarate, Probucol, Arbidol HCl, S-(+)-Rolipram, Tebipenem pivoxil (L-084), Dichlorphenamide (Diclofenamide), Aliskiren hemifumarate, DL-Carnitine hydrochloride, D-Mannitol (Osmitrol), L-carnitine (Levocarnitine), Amantadine hydrochloride (Symmetrel), Clozapine (Clozaril), Milrinone (Primacor), Mitoxantrone Hydrochloride, Novobiocin sodium (Albamycin), Ozagrel, Pancuronium (Pavulon), Propafenone (Rytmonorm), Quinine hydrochloride dihydrate, Spectinomycin hydrochloride, Xylazine HCl, L-Adrenaline (Epinephrine), DL-Adrenaline, Trospium chloride (Sanctura), Amiloride hydrochloride dihydrate, Cloxacillin sodium (Cloxacap), Zidovudine (Retrovir), Thiamphenicol (Thiophenicol), Oseltamivir phosphate (Tamiflu), Lonidamine, Peramivir Trihydrate, Carfilzomib (PR-171), Pazopanib, Fosaprepitant dimeglumine, Otilonium Bromide, Solifenacin succinate, Besifloxacin HCl (Besivance), Azilsartan Medoxomil (TAK-491), Creatinine, Adrenalone HCl, Ampiroxicam, Desloratadine, Avanafil, Bisacodyl, Methyclothiazide, Sodium Nitroprusside, Vitamin D3 (Cholecalciferol), Deferiprone, Propranolol HCl, Mefenamic acid, Ticagrelor, sulfacetamide sodium, Lomerizine HCl, Levobetaxolol HCl, Dexlansoprazole, Esmolol HCl, Eprosartan Mesylate, Histamine Phosphate, Sevelamer HCl, Deoxyarbutin, Clorprenaline HCL, Ethamsylate, Chromocarb, Mevastatin, Mexiletine HCl, Phenazopyridine HCl, (R)-(+)-Atenolol, Anisindione, Benzthiazide, Disopyramide Phosphate, Guanethidine Sulfate, Isoetharine Mesylate, Methoxamine HCl, Meticrane, Oxprenolol HCl, Pinacidil, Bendroflumethiazide, Potassium Canrenoate, Digoxigenin, Lofexidine HCl and Pindolol showed significant inhibition effect on different cancer cell lines (shown as Table 3).

Although the present invention has been described in terms of specific exemplary embodiments and examples, it will be appreciated that the embodiments disclosed herein are for illustrative purposes only, and various modifications might be made by those skilled in the art without departing from the spirit and scope of the invention as set forth in the following claims.

TABLE 3 The inhibitory effect of cardiovascular drugs on various cancer cell lines Item Name A375 HCT116 (WT) HepG2 HeLa AGS H1650 MKN-45 TSGH A549 MCF7 PC3 LoVo HL-60 Bisoprolol 117.4 118.0 107.5 110.8 80.3 80.7 79.7 87.5 123.9 111.9 95.2 118.8 85.7 Benazepril 104.0 60.0 93.0 75.9 76.7 61.6 103.3 77.5 81.8 126.1 80.7 96.0 93.6 hydrochloride Bumetanide 67.6 66.8 86.0 79.5 69.9 105.2 98.8 92.6 88.2 116.3 72.7 98.6 98.3 Furosemide (Lasix) 87.6 92.6 103.5 98.2 97.4 80.6 64.2 76.5 142.0 104.8 191.9 112.2 100.3 Trichlormethiazide 128.4 111.5 95.1 85.7 79.3 76.7 71.0 95.6 106.3 64.2 122.3 107.3 102.2 (Achletin) Aminocaproic acid 122.7 114.2 101.2 90.4 64.8 65.4 80.2 71.4 70.3 69.2 79.6 91.2 93.0 (Amicar) Indapamide (Lozol) 64.8 80.0 84.0 67.9 109.2 86.7 104.9 85.0 105.8 65.5 76.8 92.7 101.2 Simvastatin (Zocor) 114.5 124.2 113.3 103.6 85.6 114.7 79.4 101.0 126.3 81.5 91.8 99.9 69.0 Ramipril (Altace) 120.3 108.3 105.6 84.3 99.8 135.0 84.0 114.2 99.6 82.4 103.5 81.9 107.3 Fenofibrate (Tricor, 158.8 98.9 103.7 98.3 84.1 122.0 83.1 103.2 101.1 78.1 105.2 74.6 77.6 Trilipix) Acadasine 99.1 88.7 103.1 88.4 75.4 100.9 81.5 99.7 117.1 84.7 94.8 80.9 110.1 Acipimox 123.9 79.4 99.8 87.6 87.5 89.6 80.2 99.8 107.8 75.8 94.5 77.4 102.2 Ticlopidine HCl 86.5 71.9 97.4 81.9 77.2 61.6 72.7 111.5 84.9 96.8 69.9 90.5 101.8 Adiphenine HCl 87.6 133.9 95.5 96.4 109.0 118.7 95.7 82.0 86.8 102.9 102.2 95.7 105.0 Rivastigmine tartrate 76.1 117.6 93.7 90.1 63.6 83.6 93.8 83.9 65.9 67.5 85.4 85.4 103.2 (Exelon) Detomidine HCl 84.8 133.0 102.3 88.8 68.5 90.6 91.0 74.2 81.1 106.5 89.2 91.0 104.8 Gabexate mesylate 77.9 114.9 92.0 83.1 75.0 69.8 81.1 70.9 77.3 89.6 94.2 89.1 117.6 Rasagiline mesylate 76.9 141.9 92.0 88.1 75.8 71.8 87.7 74.2 91.3 88.3 103.4 94.0 104.9 S-(+)-Rolipram 77.0 86.2 90.4 69.0 69.0 73.1 69.9 81.1 71.4 80.4 89.3 94.1 107.3 Tebipenem pivoxil (L- 60.4 92.2 73.8 67.4 63.7 76.4 77.4 82.3 73.5 77.3 90.1 93.1 101.6 084) Aliskiren hemifumarate 91.2 97.2 94.2 107.8 81.8 79.8 85.1 73.3 92.0 99.1 89.0 99.5 98.5 Milrinone (Primacor) 101.4 104.1 98.5 99.0 130.3 86.2 92.9 101.1 90.9 98.5 92.0 90.5 111.8 Novobiocin sodium 93.4 115.9 92.0 96.1 128.1 93.5 84.4 85.3 95.2 109.2 89.0 87.1 123.4 (Albamycin) Ozagrel 74.7 102.5 91.2 77.7 98.5 80.6 93.9 69.4 77.7 101.8 101.4 80.6 118.3 Pancuronium (Pavulon) 75.4 101.8 92.7 83.3 119.7 91.7 95.3 68.3 100.0 110.3 107.5 79.8 108.8 Propafenone 95.8 109.2 86.0 108.8 79.8 92.5 84.7 61.1 94.1 119.7 104.4 105.3 113.2 (Rytmonorm) Xylazine HCl 63.5 100.6 83.5 65.1 86.3 67.2 88.7 61.5 71.7 104.4 105.3 96.6 116.4 L-Adrenaline 101.9 85.0 81.6 88.7 61.1 76.6 69.4 64.7 90.8 123.0 106.0 93.6 101.8 (Epinephrine) Lonidamine 65.8 81.2 114.2 61.6 69.9 65.9 93.3 86.4 109.4 86.9 102.3 96.1 115.1 Bisacodyl 88.0 122.0 100.4 89.2 107.2 93.6 132.3 104.3 66.7 65.0 83.7 85.5 96.0 Sodium Nitroprusside 78.9 125.6 85.2 107.4 96.4 109.4 115.9 106.8 110.4 97.2 76.1 70.9 81.7 Mefenamic acid 78.7 85.9 100.7 76.1 71.1 73.9 114.8 118.4 116.5 95.3 102.8 83.3 113.4 Ticagrelor 60.1 73.6 94.5 125.5 100.5 76.0 114.5 86.0 85.0 83.1 84.1 79.6 93.7 sulfacetamide sodium 64.9 76.7 98.7 75.9 81.4 79.8 117.8 120.3 70.0 110.2 70.8 81.8 111.5 Levobetaxolol HCl 76.9 70.3 99.2 88.7 62.5 69.9 118.6 98.2 75.9 85.0 77.3 80.0 107.4 Dexlansoprazole 75.1 82.8 119.8 104.7 89.8 69.6 85.8 84.9 74.5 72.1 104.5 102.0 72.2 Chromocarb 63.4 72.8 95.6 67.6 81.8 78.8 100.3 97.2 61.1 100.4 88.3 72.5 110.1 Guanethidine Sulfate 81.1 83.7 85.5 75.9 86.3 88.4 116.7 75.2 101.4 96.5 100.8 79.8 106.7 Isoetharine Mesylate 97.0 96.1 76.5 81.6 96.6 91.7 91.0 88.3 76.7 102.7 71.6 100.2

Repeated experiments for growth inhibitory effects on cancer cell lines by various cardiovascular drugs in the present invention

According to the above mentioned cardiovascular drugs for cancer growth inhibition in Table 3, the inventors took the repeat experiments for the cardiovascular drugs to check the growth inhibitory effects of cancer cells by the cardiovascular drugs. The results were showed as Table. 4.

TABLE 4 The inhibitory effect of cardiovascular drugs on various cancer cell lines AGS MKN-45 A549 H1650 TSGH-8301 T24 Amlodipine besylate 12.18342 86.43411 110.3104 110.2477 36.2492 93.07934 (Norvase) Nebivolol(Bystolic) 26.60363 52.82679 48.95406 87.37268 38.02989 97.6357 Pimobendan 60.81009 65.23876 58.25261 77.77842 59.42484 74.23873 (Vetmedin) Cilnidipine 76.93947 105.3923 67.8263 68.97714 95.88997 107.7523 Losartan potassium 74.09621 82.7996 96.04947 77.1775 91.97894 66.27541 Prazosin HCl 86.83206 70.11645 72.20906 100.6142 99.83677 88.51161 Perindopril 87.13689 73.83094 71.92761 78.569 105.3434 87.89513 Erbumine (Aceon) Nisoldipine (Sular) 64.72004 98.01894 48.91949 70.00318 77.9189 67.81543 Amlodipine 16.51631 88.19584 89.21803 72.01455 36.20415 96.56012 (Norvase) Benidipine 87.82976 92.86011 70.30445 64.52406 81.48268 60.98854 hydrochloride Azelnidipine 90.22252 139.0039 87.46658 39.65028 115.122 79.46668 Ouabain 16.61027 53.00617 15.12608 38.72274 43.58029 17.57783 Disopyramide 95.87973 110.9738 99.43989 90.5041 115.4261 87.62175 Phosphate Pitavastatin calcium 19.17312 61.30374 89.44373 49.9822 48.91635 52.63171 (Livalo) Simvastatin (Zocor) 80.96248 92.58344 109.6818 79.82892 105.9187 89.62686 Fluvastatin sodium 51.95546 65.29484 98.76315 73.07759 78.17048 71.79614 (Lescol) Atorvastatin calcium 31.48172 84.18125 90.1462 69.54683 70.58927 78.47023 (Lipitor) HepG2 Hep3B HCT116 LoVo HeLa C-33A Amlodipine besylate 95.00681 123.4192 78.25503 85.56338 101.287 33.71715 (Norvase) Nebivolol(Bystolic) 42.12209 44.81568 81.90311 85.28787 52.00985 76.97273 Pimobendan 87.23618 94.82416 53.63161 66.73545 34.00865 62.77014 (Vetmedin) Cilnidipine 77.12693 92.70906 88.59966 53.71666 64.33688 92.99393 Losartan potassium 93.9165 102.6817 105.8013 106.1105 83.41553 108.1531 Prazosin HCl 87.24 115.7343 96.42385 95.70664 90.90437 97.23898 Perindopril 99.43144 99.52974 64.99606 83.48715 66.66128 90.91624 Erbumine (Aceon) Nisoldipine (Sular) 95.50526 130.2372 77.38842 76.88917 76.89186 65.96391 Amlodipine 71.75803 99.21563 91.96059 90.33212 86.95599 38.17616 (Norvase) Benidipine 83.57118 98.76207 90.62094 69.00425 92.92617 105.186 hydrochloride Azelnidipine 100.8108 98.58296 111.283 59.86935 87.03299 123.2929 Ouabain 38.05699 33.35996 15.8664 39.68181 23.12941 35.48352 Disopyramide 108.9905 113.0039 93.97825 104.5373 102.7953 98.46569 Phosphate Pitavastatin calcium 98.05696 96.33898 35.06809 65.14687 36.90614 74.75168 (Livalo) Simvastatin (Zocor) 124.3915 113.5223 83.19968 89.30886 100.3977 112.4884 Fluvastatin sodium 104.3733 108.8002 54.97113 99.98781 54.32329 89.50117 (Lescol) Atorvastatin calcium 95.92241 91.85783 82.55431 103.0307 78.64343 96.94654 (Lipitor) MDA- NIH- PC-3 MCF-7 MB231 OVCAR-3 TOV-21G AsPC-1 Amlodipine besylate 73.55958 80.48625 82.71348 91.55643 93.54755 87.83891 (Norvase) Nebivolol(Bystolic) 36.95159 27.04214 66.43548 86.76822 86.16763 88.66097 Pimobendan 69.47215 53.94911 75.04087 74.72196 70.73536 69.30304 (Vetmedin) Cilnidipine 61.39718 64.63051 86.26857 75.85887 62.8999 57.59939 Losartan potassium 119.8879 87.64286 101.4346 98.7328 78.5729 86.43686 Prazosin HCl 100.7353 87.60617 85.08244 88.88644 91.8658 80.37522 Perindopril 81.06817 75.64154 63.78244 79.59739 71.22602 64.22167 Erbumine (Aceon) Nisoldipine (Sular) 98.90966 86.64786 74.06174 68.14248 44.35767 78.75132 Amlodipine 85.88287 63.42196 87.55328 90.31382 61.32005 89.03664 (Norvase) Benidipine 88.48559 77.28047 77.34072 85.24836 47.45143 63.35622 hydrochloride Azelnidipine 120.9111 60.82186 86.91866 102.4284 27.15468 53.57238 Ouabain 25.76337 29.14322 44.49393 42.33431 15.89529 20.08356 Disopyramide 103.4303 107.038 98.77022 102.8007 94.30529 77.1867 Phosphate Pitavastatin calcium 27.53778 83.56777 39.0358 61.40586 21.78861 51.36252 (Livalo) Simvastatin (Zocor) 92.77994 88.80292 71.08201 98.38307 63.61464 78.20757 Fluvastatin sodium 32.11203 82.4571 43.03235 84.73175 50.48937 83.55133 (Lescol) Atorvastatin calcium 56.4832 79.08152 47.83606 98.29788 34.04009 81.09956 (Lipitor) BxPC-3 SAS U2OS A375 BCC 786-O Amlodipine besylate 99.10538 94.7983 71.05736 136.6675 102.9778 73.16328 (Norvase) Nebivolol(Bystolic) 74.42236 75.56914 66.6423 44.93539 55.82216 38.30332 Pimobendan 51.86991 51.11398 56.58073 44.3967 49.56082 39.63967 (Vetmedin) Cilnidipine 68.6671 38.91442 43.14859 47.06953 60.17311 86.69656 Losartan potassium 77.73778 95.71052 105.4483 96.64672 90.16032 96.33382 Prazosin HCl 54.00243 114.3263 97.95575 77.91429 73.45319 79.5367 Perindopril 49.97129 52.47616 73.98258 83.20685 58.70789 86.19895 Erbumine (Aceon) Nisoldipine (Sular) 75.55234 48.80258 69.11154 51.46547 58.78716 49.50878 Amlodipine 86.01719 99.20403 78.90455 81.57538 74.9299 81.41545 (Norvase) Benidipine 73.78347 64.48332 54.15218 76.01467 74.60455 78.8709 hydrochloride Azelnidipine 64.6017 76.82412 69.39511 101.1726 100.2223 86.81704 Ouabain 27.01516 20.23483 22.80353 18.38812 25.61877 14.51443 Disopyramide 69.94309 96.93263 98.72214 113.872 109.7018 102.4512 Phosphate Pitavastatin calcium 59.77881 38.0374 43.44485 22.09494 26.77364 16.46038 (Livalo) Simvastatin (Zocor) 81.82199 83.91121 65.60642 78.63685 57.35253 87.7969 Fluvastatin sodium 79.10141 81.50136 91.20342 21.78962 27.03446 23.64486 (Lescol) Atorvastatin calcium 81.02839 76.29143 86.25076 23.01045 41.49497 32.53672 (Lipitor)

Claims

1. A method for treating a cancer comprising: administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a cardiovascular drug or a pharmaceutical acceptable salt thereof.

2. The method of claim 1, wherein the cardiovascular drug is selected from the group consisting of peripheral vasodilator reaming enhancer, angiotensin converting agent inhibitor, hypotension and shock therapeutic agent, diuretic, antiarrhythmic agent, antiarralciton drug, antihypertensive agent, anticoagulant thrombolytic agent, cardiac tonic, and intravenous (hemorrhoids) therapeutic agent.

3. The method of claim 2, wherein the peripheral vasodilator reaming enhancer is selected from the group consisting of Cilnidipine, Minoxidil, Prazosin HCl, Sildenafil citrate, Tadalafil (Cialis), Nicorandil (Ikorel), Lacidipine (Lacipil, Motens), Benidipine hydrochloride, Cilazapril monohydrate (Inhibace), Fosinopril sodium (Monopril), Almotriptan malate (Axert), Milrinone (Primacor), Avanafil, Lomerizine HCl, Histamine Phosphate, Chromocarb, and Pinacidil.

4. The method of claim 2, wherein the angiotensin converting agent inhibitor is selected from the group consisting of Benazepril hydrochloride, Losartan potassium, Perindopril Erbumine (Aceon), Irbesartan (Avapro), Candesartan (Atacand), Olmesartan medoxomil (Benicar), Enalaprilat dehydrate, Telmisartan (Micardis), Ramipril (Altace), Valsartan (Diovan), Enalapril maleate (Vasotec), Candesartan cilexetil (Atacand), Conivaptan HCl (Vaprisol), Azilsartan Medoxomil (TAK-491), and Eprosartan Mesylate.

5. The method of claim 2, wherein the hypotension and shock therapeutic agent is selected from the group consisting of L-Adrenaline (Epinephrine), DL-Adrenaline, and Methoxamine HCl.

6. The method of claim 2, wherein the diuretic is selected from the group consisting of Bumetanide, Furosemide (Lasix), Metolazone(Zaroxolyn), Silodosin (Rapaflo), Chlorothiazide, Trichlormethiazide (Achletin), Torsemide (Demadex), Hydrochlorothiazide, Indapamide (Lozol), Dichlorphenamide (Diclofenamide), Amiloride hydrochloride dehydrate, Solifenacin succinate, Methyclothiazide, Benzthiazide, Meticrane, Bendroflumethiazide, and Potassium Canrenoate.

7. The method of claim 2, wherein the antiarrhythmic agent is selected from the group consisting of Adenosine (Adenocard), Dofetilide (Tikosyn), Amiodarone HCl, Ibutilide fumarate, Propafenone (Rytmonorm), and Disopyramide Phosphate.

8. The method of claim 2, wherein the antiarralciton drug is selected from the group consisting of Dexrazoxane Hydrochloride, Ranolazine dihydrochloride, Nisoldipine (Sular), Ranolazine (Ranexa), Acadesine, Nifedipine (Adalat), Amlodipine besylate (Norvasc), Diltiazem HCl (Tiazac), Ticagrelor, and Oxprenolol HCl.

9. The method of claim 2, wherein the antihypertensive agent is selected from the group consisting of Bisoprolol, Doxazosin mesylate, Alfuzosin hydrochloride (Uroxatral), Nebivolol (Bystolic), Reserpine, Methyldopa (Aldomet), Eplerenon, Nimodipine (Nimotop), Betaxolol hydrochloride (Betoptic), Carvedilol, Metoprolol tartrate, Felodipine (Plendil), Amlodipine (Norvasc), Phentolamine mesilate, Imidapril (Tanatril) HCl, Aliskiren hemifumarate, Sodium Nitroprusside, Propranolol HCl, Levobetaxolol HCl, Esmolol HCl, (R)-(+)-Atenolol, Guanethidine Sulfate, and Lofexidine HCl.

10. The method of claim 2, wherein the anticoagulant thrombolytic agent is selected from the group consisting of Prasugrel (Effient), Cilostazol, Nafamostat mesylate, Clopidogrel (Plavix), Apixaban, Aminocaproic acid (Amicar), Dipyridamole (Persantine), Phenindione (Rectadione), Ticlopidine HCl, Ozagrel HCl, Argatroban, Bexarotene, Gabexate mesylate, and Ozagrel and Anisindione.

11. The method of claim 2, wherein the cardiac tonic is selected from the group consisting of Pimobendan (Vetmedin), Ampiroxicam, Digoxigenin, and Pindolol.

12. The method of claim 2, wherein the intravenous (hemorrhoids) therapeutic agent is selected from the group consisting of Edaravone (MCI-186), Daidzein, Ginkgolide A, and Bisacodyl.

13. The method of claim 1, wherein the cancer is selected from the group consisting of lung cancer, intestinal cancer, colorectal cancer, prostate cancer, liver cancer, bladder cancer, cervical cancer, breast cancer, and blood cancer.