Oleandrin induces DNA damage responses in cancer cells by suppressing the expression of Rad51
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Zhengqiang Bao1,2, Baoping Tian1, Xiaohui Wang2, Hanrong Feng2, Ye Liang2, Zhihua Chen1, Wen Li1, Huahao Shen1,3, Songmin Ying1,2
1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou 310009, China
2Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China
3State Key Laboratory of Respiratory Diseases, Guangzhou, Guangdong 510120, China
Songmin Ying, email: [email protected]
Keywords: oleandrin, DNA damage response, DNA replication, apoptosis, single strand break repair
Received: February 06, 2016 Accepted: July 09, 2016 Published: July 20, 2016
Oleandrin is a monomeric compound extracted from leaves and seeds of Nerium oleander. It had been reported that oleandrin could effectively inhibit the growth of human cancer cells. However, the specific mechanisms of the oleandrin-induced anti-tumor effects remain largely unclear. Genomic instability is one of the main features of cancer cells, it can be the combined effect of DNA damage and tumour-specific DNA repair defects. DNA damage plays important roles during tumorigenesis. In fact, most of the current chemotherapy agents were designed to kill cancer cells by inducing DNA damage. In this study, we found that oleandrin was effective to induce apoptosis in cancer cells, and cause rapid DNA damage response, represented by nuclear RPA (Replication Protein A, a single strand DNA binding protein) and γH2AX(a marker for DNA double strand breaks) foci formation. Interestingly, expression of RAD51, a key protein involved in homologous recombination (HR), was suppressed while XRCC1 was up-regulated in oleandrin treated cancer cells. These results suggested that XRCC1 may play a predominant role in repairing oleandrin-induced DNA damage. Collectively, oleandrin may be a potential anti-tumor agent by suppressing the expression of Rad51.
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