A novel STAT3 inhibitor HO-3867 induces cell apoptosis by reactive oxygen species-dependent endoplasmic reticulum stress in human pancreatic cancer cells

被引:25
作者
Hu, Yan [1 ,2 ,3 ]
Zhao, Chengguang [2 ]
Zheng, Hailun [2 ]
Lu, Kongqin [2 ]
Shi, Dengjian [2 ]
Liu, Zhiguo [2 ]
Dai, Xuanxuan [3 ]
Zhang, Yi [3 ]
Zhang, Xiuhua [3 ]
Hu, Wanle [1 ]
Liang, Guang [2 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Coloproctol, Wenzhou 325000, Peoples R China
[2] Wenzhou Med Univ, Sch Pharmaceut Sci, Chem Biol Res Ctr, Wenzhou, Peoples R China
[3] Wenzhou Med Univ, Affiliated Hosp 1, Dept Pharm, Wenzhou 325035, Peoples R China
关键词
endoplasmic reticulum stress; HO-3867; pancreatic cancer; reactive oxygen species; signal transducer and activator of transcription 3; DOWN-REGULATION; ER STRESS; FEEDBACK ACTIVATION; OVARIAN-CARCINOMA; DRUG-RESISTANCE; STATISTICS; SUPPRESSES; PI3K/AKT; PATHWAY; ACID;
D O I
10.1097/CAD.0000000000000470
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pancreatic cancer is the most commonly diagnosed malignancy among solid tumors and has shown an increasing trend year by year. Thus, there is an urgent need for the discovery of new anticancer drugs for the treatment of pancreatic cancer. In recent years, it has been reported that the compound HO-3867, a novel analog of the natural product curcumin, showed antitumor activity with low toxicity. However, the underlying mechanism of this compound's attack on cancer cells is not very clear. In the present study, it was found that HO-3867 showed good antitumor activity at the concentration of 2 mu mol/l in PANC-1 and BXPC-3 cells. Importantly, it was also found that HO-3867 treatment significantly induced reactive oxygen species (ROS) production in human pancreatic cancer cell lines, inducing PANC-1 and BXPC-3 cells. Co-treatment with the ROS scavenger, N-acetyl cysteine, partially abrogated HO-3867-induced cell apoptosis. The activation of mitogen-activated protein kinase and endoplasmic reticulum stress indicated a downstream event of ROS generation in mediating the anticancer effect of the HO-3867. In addition, independent of the ROS pathway, direct STAT3 inhibition was observed in HO-3867-induced cell apoptosis. Taken together, the results of this work suggest that both the ROS-dependent ER stress and STAT3 pathways were implicated in the cell apoptosis induced by the novel compound HO-3867. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
引用
收藏
页码:392 / 400
页数:9
相关论文
共 50 条
  • [21] Chelerythrine induces apoptosis via ROS-mediated endoplasmic reticulum stress and STAT3 pathways in human renal cell carcinoma
    He, Hongchao
    Zhuo, Ran
    Dai, Jun
    Wang, Xiaojing
    Huang, Xin
    Wang, Haofei
    Xu, Danfeng
    JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2020, 24 (01) : 50 - 60
  • [22] The combination of arsenic and cryptotanshinone induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in breast cancer cells
    Zhang, Yan Fang
    Zhang, Min
    Huang, Xu Lei
    Fu, Yu Jie
    Jiang, Yu Han
    Bao, Ling Ling
    Maimaitiyiming, Yasen
    Zhang, Guang Ji
    Wang, Qian Qian
    Naranmandura, Hua
    METALLOMICS, 2015, 7 (01) : 165 - 173
  • [23] Chitosan Oligosaccharides Induce Apoptosis in Human Renal Carcinoma via Reactive-Oxygen-Species-Dependent Endoplasmic Reticulum Stress
    Zhai, Xingchen
    Yuan, Shoujun
    Yang, Xin
    Zou, Pan
    Li, Linna
    Li, Guoyou
    Shao, Yong
    Abd El-Aty, A. M.
    Hacimuftuoglu, Ahmet
    Wang, Jing
    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2019, 67 (06) : 1691 - 1701
  • [24] Diterpenoid DGA induces apoptosis via endoplasmic reticulum stress caused by changes in glycosphingolipid composition and inhibition of STAT3 in glioma cells
    Kong, Tingting
    He, Zhenxue
    Wang, Shuying
    Jiang, Chunxin
    Zhu, Fei
    Gao, Jingjing
    Li, Liu
    Wang, Yanping
    Xie, Qing
    Li, Yunsen
    BIOCHEMICAL PHARMACOLOGY, 2022, 205
  • [25] Wogonin Induces Reactive Oxygen Species Production and Cell Apoptosis in Human Glioma Cancer Cells
    Tsai, Cheng-Fang
    Yeh, Wei-Lan
    Huang, Ssu Ming
    Tan, Tzu-Wei
    Lu, Dah-Yuu
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2012, 13 (08): : 9877 - 9892
  • [26] Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer
    Yang, Liguo
    Zhou, Xiaoshu
    Sun, Jinrui
    Lei, Qianghui
    Wang, Qi
    Pan, Di
    Ding, Mingxing
    Ding, Yi
    CELL DEATH & DISEASE, 2020, 11 (09)
  • [27] Melatonin Induces Autophagy via Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress Pathway in Colorectal Cancer Cells
    Chok, Kian Chung
    Koh, Rhun Yian
    Ng, Ming Guan
    Ng, Pei Ying
    Chye, Soi Moi
    MOLECULES, 2021, 26 (16):
  • [28] Curcumin induces apoptosis in human lung adenocarcinoma A549 cells through a reactive oxygen species-dependent mitochondrial signaling pathway
    Chen, Qingyong
    Wang, Yanyi
    Xu, Kedi
    Lu, Guohua
    Ying, Zheng
    Wu, Lijun
    Zhan, Jianwei
    Fang, Rui
    Wu, Yuquan
    Zhou, Jianying
    ONCOLOGY REPORTS, 2010, 23 (02) : 397 - 403
  • [29] MHY446 induces apoptosis via reactive oxygen species-mediated endoplasmic reticulum stress in HCT116 human colorectal cancer cells
    Ahn, Yu Ra
    Jang, Jung Yoon
    Kang, Yong Jung
    Oh, Hye Jin
    Kang, Min Kyung
    Yoon, Dahye
    Kim, Hyung Sik
    Moon, Hyung Ryong
    Chung, Hae Young
    Kim, Nam Deuk
    JOURNAL OF CHEMOTHERAPY, 2024, 36 (06) : 483 - 500
  • [30] Generation of Reactive Oxygen Species and Endoplasmic Reticulum Stress by Dictyopteris undulata Extract Leads to Apoptosis in Human Melanoma Cells
    Kim, Joon Ki
    Kang, Kyoung Ah
    Piao, Mei Jing
    Kumara, Madduma Hewage Susara Ruwan
    Jeong, Yong Joo
    Ko, Mi Hee
    Hyun, Jin Won
    JOURNAL OF ENVIRONMENTAL PATHOLOGY TOXICOLOGY AND ONCOLOGY, 2015, 34 (03) : 191 - 200