Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production

被引:73
作者
Liang, Xiaohui [1 ]
Wang, Ping [1 ]
Yang, Chun [1 ]
Huang, Fei [1 ]
Wu, Hui [1 ]
Shi, Hailian [1 ]
Wu, Xiaojun [1 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med,SATCM Key Lab New Resources, Shanghai Key Lab Compound Chinese Med, Minist Educ MOE,Key Lab Standardizat Chinese Med, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
galangin; gastric cancer; apoptosis; proliferation; ROS; stat3; CELLS; APOPTOSIS; ACTIVATION; AUTOPHAGY; PATHWAY; SIGNAL;
D O I
10.3389/fphar.2021.646628
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Galangin, a flavonoid isolated from the rhizome of Alpinia officinarum (Hance), exerts anticancer activities against many cancer cells such as liver cancer, breast cancer, lung cancer and esophageal cancer. However, the effect, as well as the underlying molecular mechanism of galangin on gastric cancer remains to be elucidated. In the present study, galangin inhibited cell viability of MGC 803 cells but not normal gastric mucosal epithelial GES-1 cells. It suppressed cell proliferation accompanied by reduced Ki67 and PCNA expression, promoted apoptosis shown by decreased Bcl-2 and elevated cleaved caspase-3 and cleaved PARP. And, galangin significantly inactivated JAK2/STAT3 pathway. When STAT3 was overexpressed, the proliferation inhibition and apoptosis promotion induced by galangin were abrogated. Meanwhile, galangin increased ROS accumulation, and reduced Nrf2 and NQO-1, but elevated HO-1 in MGC 803 cells. NAC, a ROS scavenger, rescued ROS over-accumulation and proliferation inhibition of galangin. STAT3 overexpression also counteracted excessive ROS accumulation induced by galangin. Consistent with the in vitro experiments, in nude mice exnografted with MGC 803 cells, galangin inhibited tumor growth and reversed the abnormally expressed proteins, such as p-JAK2, p-STAT3, Bcl-2, cleaved caspase-3, cleaved PARP, and Ki67. Taken together, galangin was suggested to inhibit the growth of MGC 803 cells through inducing apoptosis and decreasing cell proliferation, which might be mediated by modulating STAT3/ROS axis. Our findings implicate a potential application of galangin for gastric cancer therapy possibly with low toxicity.
引用
收藏
页数:13
相关论文
共 33 条
[21]   Cadmium induces apoptosis in human embryonic kidney (HEK) 293 cells by caspase-dependent and -independent pathways acting on mitochondria [J].
Mao, Wei-Ping ;
Ye, Ji-Lin ;
Guan, Zheng-Bing ;
Zhao, Jie-Ming ;
Zhang, Chao ;
Zhang, Na-Na ;
Jiang, Ping ;
Tian, Ting .
TOXICOLOGY IN VITRO, 2007, 21 (03) :343-354
[22]   Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals [J].
Prasad, Sandeo ;
Gupta, Subash C. ;
Tyagi, Amit K. .
CANCER LETTERS, 2017, 387 :95-105
[23]   Synergistic anti-cancer effects of galangin and berberine through apoptosis induction and proliferation inhibition in oesophageal carcinoma cells [J].
Ren, Kewei ;
Zhang, Wenzhe ;
Wu, Gang ;
Ren, Jianzhuang ;
Lu, Huibin ;
Li, Zongming ;
Han, Xinwei .
BIOMEDICINE & PHARMACOTHERAPY, 2016, 84 :1748-1759
[24]   Piperlongumine inhibits gastric cancer cells via suppression of the JAK1,2/STAT3 signaling pathway [J].
Song, Baoji ;
Zhan, Hongjie ;
Bian, Quan ;
Gu, Junping .
MOLECULAR MEDICINE REPORTS, 2016, 13 (05) :4475-4480
[25]   PLOD2 increases resistance of gastric cancer cells to 5-fluorouracil by upregulating BCRP and inhibiting apoptosis [J].
Wang, Xiaohui ;
Guo, Jiaojiao ;
Dai, Meng ;
Wang, Tengqi ;
Yang, Tingting ;
Xiao, Xuejun ;
Tang, Qi ;
Zhang, Lingli ;
Jia, Lizhou .
JOURNAL OF CANCER, 2020, 11 (12) :3467-3475
[26]   Cardamonin exerts anti-gastric cancer activity via inhibiting LncRNA-PVT1-STAT3 axis [J].
Wang, Zheng ;
Tang, Xiaoli ;
Wu, Xiaoqing ;
Yang, Meiyuan ;
Wang, Wei ;
Wang, Liuhua ;
Tang, Dong ;
Wang, Daorong .
BIOSCIENCE REPORTS, 2019, 39
[27]   The role for autophagy in cancer [J].
White, Eileen .
JOURNAL OF CLINICAL INVESTIGATION, 2015, 125 (01) :42-46
[28]   Sesamolin exerts anti-proliferative and apoptotic effect on human colorectal cancer cells via inhibition of JAK2/STAT3 signaling pathway [J].
Wu, Di ;
Wang, Xin-Ping ;
Zhang, Wei .
CELLULAR AND MOLECULAR BIOLOGY, 2019, 65 (06) :96-100
[29]   Silica nanoparticles induced intrinsic apoptosis in neuroblastoma SH-SY5Y cells via CytC/Apaf-1 pathway [J].
Yang, Yanyan ;
Yu, Yongbo ;
Wang, Jiahui ;
Li, Yanbo ;
Li, Yang ;
Wei, Jia ;
Zheng, Tong ;
Jin, Minghua ;
Sun, Zhiwei .
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, 2017, 52 :161-169
[30]   The role of STAT3 in autophagy [J].
You, Liangkun ;
Wang, Zhanggui ;
Li, Hongsen ;
Shou, Jiawei ;
Jing, Zhao ;
Xie, Jiansheng ;
Sui, Xinbing ;
Pan, Hongming ;
Han, Weidong .
AUTOPHAGY, 2015, 11 (05) :729-739