Inhibition of Autophagy Promotes Hemistepsin A-Induced Apoptosis via Reactive Oxygen Species-Mediated AMPK-Dependent Signaling in Human Prostate Cancer Cells

Biomolecules

Kwang-Il Park¹  Hu-Jang Lee¹  Soon-Cheol Ahn²  Kwang-Youn Kim³  Sang-Chan Kim⁴  Seung-Hee Yeom⁵  Young-Woo Kim⁵  Un-Jung Yun⁵ 

[1] College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea;Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 50612, Korea;Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Korea;Medical Research Center, College of Oriental Medicine, Daegu Haany University, Gyeongsan 38610, Korea;School of Korean Medicine, Dongguk University, Gyeongju 38066, Korea;

关键词: Hemistepsin A;    AMPK;    ROS;    autophagy;    apoptosis;    prostate cancer;   

DOI  :  10.3390/biom11121806

来源: DOAJ

【 摘 要 】

Chemotherapy is an essential strategy for cancer treatment. On the other hand, consistent exposure to chemotherapeutic drugs induces chemo-resistance in cancer cells through a variety of mechanisms. Therefore, it is important to develop a new drug inhibiting chemo-resistance. Although hemistepsin A (HsA) is known to have anti-tumor effects, the molecular mechanisms of HsA-mediated cell death are unclear. Accordingly, this study examined whether HsA could induce apoptosis in aggressive prostate cancer cells, along with its underlying mechanism. Using HsA on two prostate cancer cell lines, PC-3 and LNCaP cells, the cell analysis and in vivo xenograft model were assayed. In this study, HsA induced apoptosis and autophagy in PC-3 cells. HsA-mediated ROS production attenuated HsA-induced apoptosis and autophagy after treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, autophagy inhibition by 3-MA or CQ is involved in accelerating the apoptosis induced by HsA. Furthermore, we showed the anti-tumor effects of HsA in mice, as assessed by the reduced growth of the xenografted tumors. In conclusion, HsA induced apoptosis and ROS generation, which were blocked by protective autophagy signaling.

【 授权许可】

Unknown