Induction of G2/M Cell Cycle Arrest via p38/p21Waf1/Cip1-Dependent Signaling Pathway Activation by Bavachinin in Non-Small-Cell Lung Cancer Cells
Authors
Jih-Tung Pai
Division of Hematology and Oncology, Tao-Yuan General Hospital, Ministry of Health and Welfare, Taoyuan City 33004, Taiwan; [email protected]
Ming-Wei Hsu
Department of Nutritional Science, Fu Jen Catholic University, New Taipei City 24205, Taiwan; [email protected]
Yann-Lii Leu
Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan; [email protected]
Kuo-Ting Chang
Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan City 33004, Taiwan; [email protected]
Meng-Shih Weng
Department of Nutritional Science, Fu Jen Catholic University, New Taipei City 24205, Taiwan; [email protected]
Lung cancer is the most commonly diagnosed malignant cancer in the world. Non-small-cell lung cancer (NSCLC) is the major category of lung cancer. Although effective therapies have been administered, for improving the NSCLC patient’s survival, the incident rate is still high. Therefore, searching for a good strategy for preventing NSCLC is urgent. Traditional Chinese medicine (TCM) are brilliant materials for cancer chemoprevention, because of their high biological safety and low cost. Bavachinin, which is an active flavanone of Proralea corylifolia L., possesses anti-inflammation, anti-angiogenesis, and anti-cancer activities. The present study’s aim was to evaluate the anti-cancer activity of bavachinin on NSCLC, and its regulating molecular mechanisms. The results exhibited that a dose-dependent decrease in the cell viability and colony formation capacity of three NSCLC cell lines, by bavachinin, were through G2/M cell cycle arrest induction. Meanwhile, the expression of the G2/M cell cycle regulators, such as cyclin B, p-cdc2Y15, p-cdc2T161, and p-wee1, was suppressed. With the dramatic up-regulation of the cyclin-dependent kinase inhibitor, p21Waf1/Cip1, the expression and association of p21Waf1/Cip1 with the cyclin B/cdc2 complex was observed. Silencing the p21Waf1/Cip1 expression significantly rescued bavachinin-induced G2/M cell accumulation. Furthermore, the expression of p21Waf1/Cip1 mRNA was up-regulated in bavachinin-treated NSCLC cells. In addition, MAPK and AKT signaling were activated in bavachinin-added NSCLC cells. Interestingly, bavachinin-induced p21Waf1/Cip1 expression was repressed after restraint p38 MAPK activation. The inhibition of p38 MAPK activation reversed bavachinin-induced p21Waf1/Cip1 mRNA expression and G2/M cell cycle arrest. Collectively, bavachinin-induced G2/M cell cycle arrest was through the p38 MAPK-mediated p21Waf1/Cip1-dependent signaling pathway in the NSCLC cells.
Keywords: non-small-cell lung cancer (NSCLC), bavachinin, G2/M cell cycle arrest, p21Waf1/Cip1, p38 MAPK
Author Biography
Yann-Lii Leu, Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan; [email protected]
Tissue Bank, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33342, Taiwan
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