Tanshinone I induces human colorectal cancer cell apoptosis: The potential roles of Aurora A-p53 and survivin-mediated signaling pathways.
Colorectal cancer (CRC) is one of the most common malignancies worldwide and a leading cause of cancer death. Despite decades of intensive investigations, effective interventional options are still limited and patient prognosis remains poor. Tanshinone I, an active compound from traditional Chinese herbal medicine Salvia miltiorrhiza Bunge, has been shown to inhibit cell growth of leukemia, lung, and breast cancers. However, whether and how Tanshinone I exerts similar effects on CRC needs to be elucidated. Tanshinone I induced CRC cell apoptosis was characterized and the roles of Aurora A-p53 and survivin-mediated pathways were analyzed in different CRC cell lines. Tanshinone I markedly inhibited CRC cell growth and induced apoptosis in CRC cells with functional p53 protein. Interestingly, Tanshinone I did not exert as much inhibitory effect on normal colon epithelial cells or CRC cells with mutant p53, indicating relative selectivity toward colorectal cancer cells with full presence of p53. In tse cells with wild-type p53, data showed that Tanshinone I mediated Aurora A inhibition results in p53 upregulation, which is required for cell apoptosis. In CRC cells with mutant p53 protein (not able to localize to the nucleus), however, Aurora A knockdown failed to induce CRC cell apoptosis. Instead, data showed that protein level of survivin decreased following Tanshinone I treatment. These observations were further substantiated by the pivotal role of survivin in Tanshinone I mediated apoptosis in CRC cells with p53 mutant. Tanshinone I, a novel natural compound, exerts significant inhibitory effect on CRC cell growth via a mechanism involving either Aurora A-p53 axis or survivin-involving mechanism depending on different intrinsic characteristics of tumor cells.
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Mingjie
M
Lu
Department of Hematology, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214000, P.R. China.
Chen
C
Wang
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Jian
J
Wang
D045784:Abietanes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C021751:tanshinone; C576917:AURKA protein, human; D064096:Aurora Kinase A