Oncotarget

Research Papers:

Inhibited effects of CAPE-pNO2 on cervical carcinoma in vivo and in vitro and its detected metabolites

Xiaofang Yao, Hao Tang, Qiao Ren, Xiaoyan Zhao, Hua Zuo and Zhubo Li _

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Oncotarget. 2017; 8:94197-94209. https://doi.org/10.18632/oncotarget.21617

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Abstract

Xiaofang Yao1,2, Hao Tang1, Qiao Ren1, Xiaoyan Zhao1, Hua Zuo1 and Zhubo Li1

1College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China

2International Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, China

Correspondence to:

Zhubo Li, email: lizhubo2004@163.com

Keywords: caffeic acid p-nitro phenethyl ester (CAPE-pNO2), cervical cancer cells, endogenous apoptosis pathway, xenograft, metabolites

Received: June 21, 2017    Accepted: August 27, 2017    Published: October 07, 2017

ABSTRACT

The development of advanced cervical cancer therapies is a particularly urgent need due to the strong side effects and toxicities of current treatments. Caffeic acid phenethyl ester (CAPE) exhibits broad-spectrum antitumor activities and little toxicity or side effects. In our previous study, caffeic acid para-nitro phenethyl ester (CAPE-pNO2) significantly improved the effect of anti-platelet aggregation and attenuated myocardial ischemia. Based on this finding, we aimed to further explore the antitumor activity of CAPE-pNO2 in cervical cancer cells and tumor xenografts. In addition, we assessed the biotransformation of CAPE-pNO2 in cervical cancer cells. Our study demonstrated that both CAPE and CAPE-pNO2 can inhibit cell proliferation via the induction of G2/M cell cycle arrest. More importantly, CAPE-pNO2 dramatically induced cell apoptosis via significant down-regulation of pro-caspase-3, pro-caspase-9, Bcl-2, Cyclin B1 and Cdc2 and up-regulation of cleaved-caspase-3, Bax, CytoC and P21Cip1. Moreover, CAPE and CAPE-pNO2 significantly suppressed the growth and angiogenesis of nude mice xenografts. CAPE and CAPE-pNO2 were found to degrade into four and six metabolites, respectively. The metabolites of CAPE and CAPE-pNO2 were different, and the major metabolic pathway may be phase II reactions. These results suggest that CAPE-pNO2 induced cell apoptosis and cell cycle arrest via a strong regulatory effect on relevant apoptotic proteins. Therefore, CAPE-pNO2 should be further studied as a potent anti-cancer agent.


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