Different responses of HepG2 subclones to low dose ethaselen

doi:10.5246/jcps.2016.04.034

Journal of Chinese Pharmaceutical Sciences ›› 2016, Vol. 25 ›› Issue (4): 302-309.DOI: 10.5246/jcps.2016.04.034

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Different responses of HepG2 subclones to low dose ethaselen

Guozhou Zhang, Kun Xiong, Weiwei Ma, Wei Xu, Huihui Zeng^*

State Key Laboratory of Natural and Biomimetic Drugs; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2015-11-27 Revised:2015-12-25 Online:2016-04-21 Published:2015-12-28
Contact: Tel.: 86-10-82802878, Fax: 86-10-62015584, E-mail: zenghh@bjmu.edu.cn
Supported by:
National Natural Science Foundation (Grant No. 81372266) and National Science and Technology Major Project, People’s Republic of China (Grant No. 2011zx09101-001-03).

Abstract

Abstract:

As a synthesized antineoplastic organoselenium compound, ethaselen is known to induce apoptosis in tumor cells via dose-dependent thioredoxin reductase (TrxR) inhibition. Thioredoxin, the multifunctional biological substrate of TrxR, is then left in the oxidized state, which subsequently leads to intracellular accumulation of reactive oxygen species (ROS), cell cycle arrest and/or apoptosis. However, the low dose effect of ethaselen remains largely unknown. Several subclones have been derived from HepG2 cells by using single cell or colony isolation. The low dose of ethaselen was defined as the drug concentration of retaining >90% HepG2 cells alive. The HepG2 cells were used as reference of its subclones (SM01, SM02 and SM03), and the cell cycle transition, intracellular proteins change, colony formation and sphere growth were assayed in treatment of low dose ethaselen. HepG2 and its subclones differently responded to lethal dose of cisplatin or 5-fluorouracil. Low dose of ethaselen (1 µm) modulated the cell cycle transition at 12 h of treatment, but cells were partially recovered at 24 h of treatment though some proteins were still affected. Low dose of ethaselen did not inhibit the small colony (diameter >100 µm) formation and sphere growth of HepG2 and SM01. However, low dose of ethaselen could specifically inhibit the survival, large colony (diameter >500 µm) formation and sphere growth of SM03, although SM03 could be rapidly recovered from ethaselen-induced cell cycle check. HepG2 and its subclone cells could survive but respond differently to treatment of low dose ethaselen (1 µM). Low dose of ethaselen could significantly inhibit a HepG2 subclone (SM03) in cell survival and colony growth.

Key words: Low dose, Organoselenium, Cell subcloning, Heterogeneity, Tumor cell

CLC Number:

R916.3

Supporting:

Guozhou Zhang, Kun Xiong, Weiwei Ma, Wei Xu, Huihui Zeng. Different responses of HepG2 subclones to low dose ethaselen[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(4): 302-309.

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Different responses of HepG2 subclones to low dose ethaselen

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