Shikonin regulates HeLa cell death via caspase-3 activation and blockage of DNA synthesis

Journal of Asian Natural Products Research
Zhen WuTakashi Ikejima

Abstract

Shikonin, isolated from the plant Lithospermum erythrorhizon Sieb. ET Zucc, inhibited tumor cell growth and induced cell death in various tumor cells, with 50% growth inhibition of human cervical cancer cells, HeLa, at 18.9 +/- 1.1 mumol L-1. Treated with 40 mumol L-1 shikonin, HeLa cells underwent marked apoptotic morphological changes such as a round shape, membrane blebbing and apoptotic bodies derived from the fragmented nuclei. Another hallmark of apoptosis, DNA fragmentation, was observed by gel electrophoresis. Shikonin (10 mumol L-1) significantly blocked the transition from G1 to S phase in the HeLa cell cycle. Pan-caspase inhibitor (Z-VAD-FMK), caspase-3 inhibitor (Z-DEVD-FMK) or caspase-8 inhibitor (Z-IETD-FMK) effectively inhibited shikonin-induced cell death, while caspase-1 inhibitor (Ac-YVAD-CMK) and caspase-9 inhibitor (Z-LEHD-FMK) failed to affect cell death. Caspase-3 activity significantly increased within 12 h after shikonin treatment. Reduced expression of inhibitor of caspase-activated deoxyribonuclease (ICAD) after exposure to shikonin for 12 h suggests the resultant activation of caspase-activated deoxyribonuclease (CAD), leading to apoptosis.

References

Sep 1, 1977·Chemical & Pharmaceutical Bulletin·U SankawaH Otsuka
Mar 17, 1995·Journal of Medicinal Chemistry·B Z AhnB D Hwang
Feb 7, 1997·Cell·S Nagata
Mar 4, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·O MeilhacA Négre-Salvayre
Oct 14, 2000·Cell Biology and Toxicology·H S ZhuL Chen
May 30, 2002·Biological & Pharmaceutical Bulletin·Kenroh SasakiFumihiko Yoshizaki
Oct 25, 2002·International Journal of Cancer. Journal International Du Cancer·Hongbo HuKyung-Sun Kang

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Citations

Jul 23, 2011·Chinese Medicine·Wen TanYitao Wang
Mar 27, 2012·Annals of Surgical Oncology·Ching-Hsein ChenJen-Tsung Yang
Dec 2, 2006·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yue HouMinghong Zhao
Apr 29, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Morteza Eskandani, Hossein Nazemiyeh
Aug 8, 2009·Biomedical Chromatography : BMC·MeiXiang ZhuYuFen Zhao
Sep 22, 2012·Journal of Ethnopharmacology·Seetharaman RajasekarYoung Whan Choi
Jul 3, 2016·Archives of Oral Biology·Da Jeong KimYoung Whan Choi
Oct 4, 2011·Critical Reviews in Oncology/hematology·Wei WuJianyong Li
Nov 7, 2013·Pharmaceutical Biology·Long SuYang Zhang
Jan 24, 2009·International Journal of Cancer. Journal International Du Cancer·Huanjie YangJinbao Liu
Apr 30, 2015·Journal of the Chinese Medical Association : JCMA·Muhammad Daniyal, Muhammad Akram
Jan 9, 2019·BMC Cancer·Shoude ZhangZhanhai Su
May 22, 2007·Molecular Cancer Therapeutics·Weidong HanXun Hu
Nov 6, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Miao-Miao LiuZhao-Jun Wei

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