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Cancer Chemother Pharmacol. 2017 Jul;80(1):91-100. doi: 10.1007/s00280-017-3337-2. Epub 2017 Jun 8.

The cardiac glycoside oleandrin induces apoptosis in human colon cancer cells via the mitochondrial pathway.

Author information

1
Department of Pharmacy, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
2
Department of Clinical Laboratory, Hospital of Integrated Chinese and Western Medicine, Southern Medical University, Guangzhou, 510315, China.
3
Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.
4
Department of Pharmacy, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China. wangcx@smu.edu.cn.
5
Guangdong Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, 510515, People's Republic of China. wangcx@smu.edu.cn.
6
Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China. fandeng@smu.edu.cn.

Abstract

PURPOSE:

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.

METHODS:

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 Ca2+ was determined using Fluo-3 AM,glutathione (GSH) levels were measured using a GSH detection kit,and the activity of caspase-3, -9 was measured using a peptide substrate. BAX, pro-caspase-3, -9, cytochrome C and BCL-2 expression were determined by Western blotting.

RESULTS:

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 Ca2+ concentration, but decreased GSH concentration in the cells.

CONCLUSIONS:

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.

KEYWORDS:

Apoptosis; Cardiac glycosides; Human colon cancer; Oleandrin

PMID:
28597038
DOI:
10.1007/s00280-017-3337-2
[Indexed for MEDLINE]

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