title: Nujiangexathone A, a Novel Compound Derived from Garcinia nujiangensis, Induces Caspase-Dependent Apoptosis in Cervical Cancer through the ROS/JNK Pathway.
abstract: Nujiangexathone A (NJXA), a novel compound derived fromGarcinia 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, cytochromecrelease, 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.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, China. zhangli1003ecpu@126.com.|Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital, No. 540, Xinhua Road, Shanghai 201203, China. zhangli1003ecpu@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, China. mo2jiaojiaozhu@163.com.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Kong
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, China. bishopjiaozhu@gmail.com.
authors.forename: Zhao-Qing
authors.initials: ZQ
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, China. diablo2_joe@163.com.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, China. fjlfreda@hotmail.com.
authors.forename: Ji-Ling
authors.initials: JL
authors.lastname: Feng
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, China. ths97029@163.com.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Tan
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, China. laurence.ylao@gmail.com.
authors.forename: Yuan-Zhi
authors.initials: YZ
authors.lastname: Lao
authors.affiliation: Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital, No. 540, Xinhua Road, Shanghai 201203, China. 13701888178@163.com.
authors.forename: Lian-Bo
authors.initials: LB
authors.lastname: Xiao
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, China. xuhongxi88@gmail.com.|Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital, No. 540, Xinhua Road, Shanghai 201203, China. xuhongxi88@gmail.com.
authors.forename: Hong-Xi
authors.initials: HX
authors.lastname: Xu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D029760:Garcinia / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D020169:Caspases
keywords: JNK; Nujiangexathone A; ROS; apoptosis; cervical cancer