Shikonin differentially regulates glucose metabolism via PKM2 and HIF1α to overcome apoptosis in a refractory HCC cell line

Life Sciences
Wei YangYahui Liu

Abstract

In tumor cells, shikonin treatment has been reported to inhibit glycolysis by suppressing the activity of pyruvate kinase M2 (PKM2) and to induce apoptosis by increasing reactive oxygen species (ROS) production. However, hepatocellular carcinoma (HCC) shows variable sensitivity to shikonin treatment, and the mechanism for these differences remains unclear. We evaluated the effects of shikonin on metabolic and oxidative pathways in sensitive and refractory HCC cell lines to identify mechanisms of differential sensitivity. Cell viability and apoptosis were evaluated by MTT assay, PI/Annexin V and JC-1 staining. Mitochondrial function was further evaluated by measurements of ROS and mitochondrial mass. Oxygen consumption rates, NAD+/NADH, ATP and lactate were measured as indicators of energy metabolism and glycolysis. Protein expression associated with glycolysis and apoptosis was evaluated by western blotting, RT-qPCR and immunofluorescence staining. The sensitivity to shikonin treatment was significantly higher for HepG2 cells than for HCCLM3 cells, with less dramatic effects in HCCLM3 cells on apoptosis, ROS, and oxidative phosphorylation. Shikonin up-regulated mitochondrial biogenesis to increase mitochondrial oxidative phosph...Continue Reading

References

Jan 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Xiaoyu LinYu Shen
Dec 17, 2008·Annals of the New York Academy of Sciences·Richard C Scarpulla
Mar 17, 2009·The American Journal of Pathology·Thomas AmannClaus Hellerbrand
Mar 15, 2011·Cancer Cell·Lydia W S FinleyMarcia C Haigis
Dec 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hung-Jung WangWen-Ching Wang
Jul 20, 2014·Trends in Biochemical Sciences·Krushna C Patra, Nissim Hay
Mar 23, 2017·Journal of Experimental & Clinical Cancer Research : CR·Dong XuHonglei Jiang
Sep 12, 2017·Antioxidants & Redox Signaling·Chandra K SinghNihal Ahmad
Sep 25, 2017·International Journal of Cancer. Journal International Du Cancer·Stefan Rodic, Mark David Vincent
Jun 3, 2018·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Philippe IcardHubert Lincet
Dec 14, 2018·Oxidative Medicine and Cellular Longevity·Serena De MatteisAnna Maria Giudetti
Mar 8, 2019·Cancer Science·Yoshihiro HayashiGang Huang
May 19, 2019·Journal of Experimental & Clinical Cancer Research : CR·Jiao FengChuanyong Guo
Jul 25, 2019·Journal of Cancer·Chien-Liang LiuShih-Ping Cheng
Apr 17, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Qiaozhu ZuoWenxin Qin

❮ Previous
Next ❯

Citations

Jul 9, 2021·Apoptosis : an International Journal on Programmed Cell Death·Xiaofeng DaiJianying Zhang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis