A novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy

Tsung I. Hsu, Ying Jung Chen, Chia Yang Hung, Yi-Ching Wang, Sin Jin Lin, Wu-Chou Su, Ming-Derg Lai, Sang Yong Kim, Qiang Wang, Keduo Qian, Masuo Goto, Yu Zhao, Yoshiki Kashiwada, Kuo Hsiung Lee, Wen Chang Chang, Jan-Jong Hung

研究成果: Article

14 引文 斯高帕斯(Scopus)

摘要

Herein, we evaluated the anti-cancer effect and molecular mechanisms of a novel betulinic acid (BA) derivative, SYK023, by using two mouse models of lung cancer driven by KrasG12D or EGFRL858R. We found that SYK023 inhibits lung tumor proliferation, without side effects in vivo or cytotoxicity in primary lung cells in vitro. SYK023 triggered endoplasmic reticulum (ER) stress. Blockage of ER stress in SYK023-treated cells inhibited SYK023-induced apoptosis. In addition, we found that the expression of cell cycle-related genes, including cyclin A2, B1, D3, CDC25a, and CDC25b decreased but, while those of p15INK4b, p16INK4a, and p21CIP1 increased following SYK023 treatment. Finally, low doses of SYK023 significantly decreased lung cancer metastasis in vitro and in vivo. Expression of several genes related to cell migration, including synaptopodin, were downregulated by SYK023, thereby impairing F-actin polymerization and metastasis. Therefore, SYK023 may be a potentially therapeutic treatment for metastatic lung cancer.

原文English
頁(從 - 到)13671-13687
頁數17
期刊Oncotarget
6
發行號15
DOIs
出版狀態Published - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

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    Hsu, T. I., Chen, Y. J., Hung, C. Y., Wang, Y-C., Lin, S. J., Su, W-C., Lai, M-D., Kim, S. Y., Wang, Q., Qian, K., Goto, M., Zhao, Y., Kashiwada, Y., Lee, K. H., Chang, W. C., & Hung, J-J. (2015). A novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy. Oncotarget, 6(15), 13671-13687. https://doi.org/10.18632/oncotarget.3701