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NK007 helps in mitigating paclitaxel resistance through p38MAPK activation and HK2 degradation in ovarian cancer
Author(s) -
Li Zhenhua,
Tang Xin,
Luo Yu,
Chen Bangyu,
Zhou Congcong,
Wu Xiuqing,
Tang Zhenping,
Qi Xiaojie,
Cao Guangchao,
Hao Jianlei,
Liu Zonghua,
Wang Qingmin,
Yin Zhinan,
Yang Hengwen
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28278
Subject(s) - paclitaxel , apoptosis , ovarian cancer , downregulation and upregulation , cancer research , chemistry , cell growth , cancer cell , programmed cell death , degradation (telecommunications) , extracellular , microbiology and biotechnology , cancer , biology , biochemistry , medicine , computer science , telecommunications , gene
Ovarian cancer resistance to available medicines is a huge challenge in dire need of a solution, which makes its recurrence and mortality rate further exacerbated. A promising approach to overcome chemoresistance is drug screening from natural products. Here, we report that NK007, a (±)‐tylophorine malate isolated from the Asclepiadaceae family, selectively inhibited the proliferation of A2780 and A2780 (Taxol) cells and migration of paclitaxel‐sensitive and ‐resistant ovarian cancer cells. Interestingly, the decline of cell viability, including cell multiplication, clonality, and migration capacity was independent on cell apoptosis. At the molecular level, NK007 considerably induced G1/S arrest and upregulated the expression of phospho‐p38 mitogen‐activated protein kinase (p‐p38MAPK). In addition, hexokinase 2 (HK2) protein degradation was considerably elevated in the presence of NK007, which resulted in the reduction of oxygen consumption rate and extracellular acidification rate. Altogether, our results indicate that NK007, an analog of tylophorine, can overcome paclitaxel (PTX) resistance through p38MAPK activation and HK2 degradation. As an effective, alternative antiresistance agent, NK007 exhibits a promising potential to treat PTX‐resistant ovarian cancer.