DNA damaging effect of SLXM-2, a derivative of cyclophosphamide, on hepatocarcinoma H22 cells in vivo

doi:10.5246/jcps.2014.01.002

Journal of Chinese Pharmaceutical Sciences ›› 2014, Vol. 23 ›› Issue (1): 16-21.DOI: 10.5246/jcps.2014.01.002

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DNA damaging effect of SLXM-2, a derivative of cyclophosphamide, on hepatocarcinoma H₂₂ cells in vivo

Mingming Chu, Xia Yuan, Xuan Jia, Ting Sun, Wei Guo, Xiao Jiang, Jingtao Liu, Runtao Li^*, Jingrong Cui^*

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

Received:2013-05-06 Revised:2013-06-15 Online:2014-01-23 Published:2014-01-22
Contact: Runtao Li*, Jingrong Cui*
Supported by:
Eleventh Five Year Plan for National Science and Technology Major Project (Grant No. 2009ZX0930010).

Abstract

Abstract:

Compound SLXM-2, a derivative of cyclophosphamide (CTX), has shown potent growth-inhibitory effect on tumor cells with low toxicity in previous studies. However, the mechanism of its anti-tumor effect, especially on DNA damage, remains largely unclear. This study investigated the effect of SLXM-2 on the survival time of mice transplanted with the ascitic fluid-type hepatocarcinoma 22 (H₂₂). We also evaluated the correlation between DNA damaging effect of SLXM-2 and its anti-tumor effect, and to probe the possible molecular mechanism for its effect on H₂₂ cells. The results suggested that SLXM-2 significantly (P<0.05) prolonged the survival time of mice bearing the ascitic fluid-type H₂₂. Furthermore, SLXM-2 induced DNA damage in a dose-dependent manner in H₂₂ cells. Further investigation revealed that SLXM-2 significantly (P<0.05) up-regulated the expression levels of a series of DNA damage-related proteins, such as γH2AX (Ser139), p-Chk1 (Ser296), p-Chk2 (Thr68), p-p53 (Ser15), p-p53 (Ser20) and p21, and down-regulated the expression of p-ATR (Ser428) and p-ATM (Ser1981). In conclusion, SLXM-2 showed a remarkable anti-tumor activity on ascitic fluid-type H₂₂ cells, and its molecular mechanism is related to its DNA damaging effect.

Key words: SLXM-2, H22, DNA damage, SCGE, DNA damage-related proteins

CLC Number:

R962

Supporting:

Mingming Chu, Xia Yuan, Xuan Jia, Ting Sun, Wei Guo, Xiao Jiang, Jingtao Liu, Runtao Li, Jingrong Cui. DNA damaging effect of SLXM-2, a derivative of cyclophosphamide, on hepatocarcinoma H₂₂ cells in vivo[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(1): 16-21.

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DNA damaging effect of SLXM-2, a derivative of cyclophosphamide, on hepatocarcinoma H₂₂ cells in vivo

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