Nujiangexathone A, a Novel Compound Derived from Garcinia nujiangensis, Induces Caspase-Dependent Apoptosis in Cervical Cancer through the ROS/JNK Pathway

Li Zhang,Zhao-Qing Zheng,Hong-Sheng Tan,Si-Yuan Kong,Ji-Ling Feng,Yuan-Zhi Lao,Xiao-Xiao Meng,Lian-Bo Xiao,Hong-Xi Xu

doi:10.3390/molecules21101360

Abstract

Nujiangexathone A (NJXA), a novel compound derived from Garcinia nujiangensis, has been demonstrated to inhibit the proliferation of several human cancer cell lines. This study is the first to demonstrate the apoptosis inductive activities of NJXA and the possible underlying mechanisms. Our results demonstrated that NJXA inhibited colony formation by HeLa and SiHa cells in a dose-dependent manner. An Annexin V-FITC/PI staining assay showed that NJXA strongly triggered apoptosis in a dose-dependent manner. Western blotting analyses showed that NJXA induced the caspase-dependent apoptosis of HeLa and SiHa cells by triggering a series of events, including changes in the levels of Bcl-2 family proteins, cytochrome c release, caspase-3 activation, and chromosome fragmentation. Furthermore, we demonstrated that NJXA induced cell apoptosis by activating the reactive oxygen species (ROS)-mediated JNK signaling pathway. Consistent with this finding, a ROS scavenger, N-acetyl-l-cysteine (NAC, 10 mM), hindered NJXA-induced apoptosis and attenuated the sensitivity of HeLa and SiHa cells to NJXA. In vivo results further confirmed that the tumor inhibitory effect of NJXA was partially through the induction of apoptosis. Taken together, our results demonstrated that NJXA induced the apoptosis of HeLa and SiHa cells through the ROS/JNK signaling pathway, indicating that NJXA could be important candidate for the clinical treatment of cervical cancer.

Highlights

Cancer is a deadly disease that kills approximately half a million people annually
The results indicated that Nujiangexathone A (NJXA) suppressed the formation of colonies by both cervical cancer cell lines in a concentration- and time-dependent manner (Figure 1)
NJXA, a novel compound isolated from nujiangensis, was investigated with regard to its potential of NJXA, a novel compound isolated from G. nujiangensis, was investigated with regard to its development as an anticancer drug for treating

Summary

Introduction

Cancer is a deadly disease that kills approximately half a million people annually. Cervical cancer is the fourth most common type of cancer in women, and approximately 80% of cervical cancers occur in developing countries [1]. The standard treatment for cervical cancer is radical pelvic surgery followed by chemotherapy. Patients are generally treated with cisplatin-based chemotherapy; adverse side effects, including nephrotoxicity, and gastrointestinal and cardiovascular damage, have limited the success of this treatment. Molecules 2016, 21, 1360 harmful side effects when used alone or in combination, and their lack of selectivity for cancer cells continues to be the greatest challenge for anticancer drug discovery [2]. There is a high demand for effective and selective pharmaceutical agents to treat cervical cancer

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Conclusion