oleandrin and Colonic-Neoplasms

Evidence indicates that the cardiac glycoside oleandrin exhibits cytotoxic activity against several different types of cancer. However, the specific mechanisms underlying oleandrin-induced anti-tumor effects remain largely unknown. The present study examined the anti-cancer effect and underlying mechanism of oleandrin on human colon cancer cells.. The cytotoxicity and IC50 of five small molecule compounds (oleandrin, neriifolin, strophanthidin, gitoxigenin, and convallatoxin) in human colon cancer cell line SW480 cells and normal human colon cell line NCM460 cells were determined by cell counting and MTT assays, respectively. Apoptosis was determined by staining cells with annexin V-FITC and propidium iodide, followed by flow cytometry. Intracellular Ca. Oleandrin significantly decreased cell viabilities in SW480, HCT116 and RKO cells. The IC50 for SW480 cells was 0.02 µM, whereas for NCM460 cells 0.56 µM. More interestingly, the results of flow cytometry showed that oleandrin potently induced apoptosis in SW480 and RKO cells. Oleandrin downregulated protein expression of pro-caspase-3, -9, but enhanced caspase-3, -9 activities. These effects were accompanied by upregulation of protein expression of cytochrome C and BAX, and downregulation of BCL-2 protein expression in a concentration-dependent manner. Furthermore, oleandrin increased intracellular Ca. The present results suggest that oleandrin induces apoptosis in human colorectal cancer cells via the mitochondrial pathway. Our findings provide new insight into the mechanism of anti-cancer property of oleandrin.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Calcium; Cardenolides; Caspase 3; Caspase 9; Cell Line; Cell Line, Tumor; Colon; Colonic Neoplasms; Dose-Response Relationship, Drug; Down-Regulation; Flow Cytometry; Glutathione; Humans; Inhibitory Concentration 50; Mitochondria; Up-Regulation

Platinum derivatives are used widely for the treatment of many cancers. However, the toxicity that is observed makes imperative the need for new drugs, or new combinations. Anvirzel™ is an extract which has been demonstrated with experimental data that displays anticancer activity. The aim of the present study is to determine whether the combination of Cisplatin and Anvirzel™ has a synergistic effect against different types of cancer.. To measure the efficacy of treatment with Cisplatin and Anvirzel™, methyl-tetrazolium dye (MTT) chemosensitivity assays were used incorporating established human cancer cell lines. Measurements were performed in triplicates, three times, using different incubation times and different concentrations of the two formulations in combination or on their own. t-test was used for statistical analysis.. In the majority of the cell lines tested, lower concentrations of Anvirzel™ induced a synergistic effect when combined with low concentrations of Cisplatin after an incubation period of 48 to 72 h. The combination of Anvirzel™/Cisplatin showed anti-proliferative effects against a wide range of tumours.. The results showed that the combination of Anvirzel™ and Cisplatin is more effective than monotherapy, even when administered at low concentrations; thus, undesirable toxic effects can be avoided.

Topics: Antineoplastic Agents; Breast Neoplasms; Cardenolides; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cisplatin; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Synergism; HCT116 Cells; Humans; Male; MCF-7 Cells; Pancreatic Neoplasms; Prostatic Neoplasms; Time Factors

Cardiac glycosides have been reported to exhibit cytotoxic activity against several different cancer types, but studies against colorectal cancer are lacking. In a screening procedure aimed at identifying natural products with activity against colon cancer, several cardiac glycosides were shown to be of interest, and five of these were further evaluated in different colorectal cancer cell lines and primary cells from patients. Convallatoxin (1), oleandrin (4), and proscillaridin A (5) were identified as the most potent compounds (submicromolar IC50 values), and digitoxin (2) and digoxin (3), which are used in cardiac disease, exhibited somewhat lower activity (IC50 values 0.27-4.1 microM). Selected cardiac glycosides were tested in combination with four clinically relevant cytotoxic drugs (5-fluorouracil, oxaliplatin, cisplatin, irinotecan). The combination of 2 and oxaliplatin exhibited synergism including the otherwise highly drug-resistant HT29 cell line. A ChemGPS-NP application comparing modes of action of anticancer drugs identified cardiac glycosides as a separate cluster. These findings demonstrate that such substances may exhibit significant activity against colorectal cancer cell lines, by mechanisms disparate from currently used anticancer drugs, but at concentrations generally considered not achievable in patient plasma.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cardenolides; Colonic Neoplasms; Digitoxin; Digoxin; Drug Screening Assays, Antitumor; HT29 Cells; Humans; Irinotecan; NF-kappa B; Proscillaridin; Strophanthins