Abstract
Curcumin, a major bioactive curcuminoid derived from the rhizome of Curcuma longa, is known to have anticancer potential and is still under investigation. In this study, we investigated the cytotoxic mechanism(s) of curcumin against acidity-tolerant prostate cancer PC-3AcT cells in lactic acid-containing medium. Using 2D-monolyer and 3D spheroid culture models, MTT assay, annexin V-PE binding assay, flow cytometric analysis, measurement of ATP content, and Western blot analysis were used for this study. At nontoxic concentrations in normal prostate epithelial RWPE-1 and HPrEC cells, curcumin led to strong cytotoxicity in PC-3AcT cells, including increases in sub-G0/G1 peak, annexin V-PE-positive cells, and ROS levels; loss of mitochondrial membrane potential; reduction of cellular ATP content; DNA damage; and concurrent induction of apoptosis and necroptosis. A series of changes induced by curcumin were effectively reversed by reducing ROS levels or replenishing ATP. Pretreatment with apoptosis inhibitor Q-VD-Oph-1 or necroptosis inhibitor necrostatin-1 restored cell viability inhibited by curcumin. Treatment of 3D spheroids with curcumin decreased cell viability, accompanied by an increase in mediators of apoptosis and necropt...Continue Reading
References
Aug 1, 1992·Mutation Research·T MoritaK Okumura
Nov 1, 1992·Carcinogenesis·M T HuangA H Conney
Aug 1, 1982·International Journal of Radiation Oncology, Biology, Physics·E M Röttinger, M Mendonca
Oct 11, 2005·Journal of Cellular Biochemistry·Shaun McKenzie, Natasha Kyprianou
Apr 14, 2006·Neoplasia : an International Journal for Oncology Research·Oliver ThewsMichael Gekle
Jul 11, 2009·The AAPS Journal·Jayaraj RavindranBharat B Aggarwal
Sep 11, 2012·Advances in Pharmacology·Kate M BaileyRobert J Gillies
Jan 19, 2013·Neuroscience Letters·Min-Chao DaiLiu-Guan Bian
Mar 8, 2013·Cancer Prevention Research·Tai-Shan ChengMing-Shyue Lee
Jan 31, 2014·The New England Journal of Medicine·Andreas Linkermann, Douglas R Green
Jun 20, 2014·Redox Biology·Theodore KalogerisRonald J Korthuis
Aug 20, 2014·Nature Reviews. Urology·Jason M FarrowChristopher P Evans
Nov 8, 2014·PloS One·Karen F ChambersMichael R Doran
Aug 15, 2015·Oxidative Medicine and Cellular Longevity·Jiahui Liu, Zhichong Wang
Oct 8, 2015·Food & Function·Li ZhangYang Sun
Oct 27, 2015·International Journal of Oncology·Yuefeng DuDalin He
Dec 29, 2015·Molecular Medicine Reports·Ruinian ZhengSenming Wang
Oct 27, 2016·Oncotarget·Hao WuXun Hu
Oct 21, 2016·Medicinal Research Reviews·Bowen KeGu He
Sep 1, 2016·Molecular Cancer Research : MCR·Yanrong QianXiaozhuo Chen
Apr 10, 2017·Redox Biology·Aida Rodriguez-GarciaRosa M Sainz
May 27, 2017·Journal of Bioenergetics and Biomembranes·Zixuan ZhangHao Liu
Nov 21, 2017·Oncotarget·Takeo KosakaMototsugu Oya
Jan 9, 2019·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Jun 20, 2019·Frontiers in Genetics·Faiz-Ul HassanChengjian Yang
Jul 31, 2019·Pathology, Research and Practice·Faezeh GhasemiHamed Mirzaei
Nov 19, 2019·Frontiers in Oncology·Karen G de la Cruz-LópezJoaquín Manzo-Merino
Feb 18, 2020·Molecular and Cellular Biochemistry·Yoon-Jin LeeSang-Han Lee
Mar 7, 2020·The Prostate·Ho Kyung SeoKyung-Chae Jeong