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Cancer Chemotherapy and Pharmacology

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08.06.2017 | Original Article

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

verfasst von: Li Pan, Yuming Zhang, Wanlu Zhao, Xia Zhou, Chunxia Wang, Fan Deng

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2017

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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.

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Titel: The cardiac glycoside oleandrin induces apoptosis in human colon cancer cells via the mitochondrial pathway
verfasst von: Li Pan
Yuming Zhang
Wanlu Zhao
Xia Zhou
Chunxia Wang
Fan Deng
Publikationsdatum: 08.06.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2017
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-017-3337-2

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Springer Medizin

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

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

Methods

Results

Conclusions

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