title: Oleandrin induces DNA damage responses in cancer cells by suppressing the expression of Rad51.
abstract: 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.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou 310009, China.|Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Zhengqiang
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Baoping
authors.initials: B
authors.lastname: Tian
authors.affiliation: Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Hanrong
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou 310009, China.|State Key Laboratory of Respiratory Diseases, Guangzhou, Guangdong 510120, China.
authors.forename: Huahao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou 310009, China.|Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Songmin
authors.initials: S
authors.lastname: Ying
mesh_terms: D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002298:Cardenolides / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D051135:Rad51 Recombinase / Q000378:metabolism*; D000076105:X-ray Repair Cross Complementing Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D002298:Cardenolides; C468783:H2AX protein, human; D006657:Histones; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D051135:Rad51 Recombinase; C021065:oleandrin
keywords: DNA damage response; DNA replication; apoptosis; oleandrin; single strand break repair