title: Nujiangexathone A, a novel compound from Garcinia nujiangensis, suppresses cervical cancer growth by targeting hnRNPK.
abstract: Cervical cancer is among the most frequently diagnosed cancers in females worldwide. Nujiangexathone A (NJXA), a novel compound from Garcinia nujiangensis, has been shown to have anti-cancer potential. In this study, the anti-tumor effects and the underlying mechanisms of NJXA action were investigated. Our results suggested that NJXA induced G0/G1 cell cycle arrest in HeLa and SiHa cells by down-regulating cyclins B1, E1, and A and cyclin-dependent kinases 2, 4 and 6, while selectively restoring p27. Using two-dimensional gel electrophoresis, we showed that NJXA reduced the expression of heterogeneous nuclear ribonucleoprotein K (hnRNPK) by accelerating ubiquitin-proteasome-dependent hnRNPK degradation, which then induced cell cycle arrest through the c-Myc-cyclin/Cdk-Rb-E2F1 pathway. The loss-of-function study showed NJXA induced cell cycle arrest was mediated by down regulation of hnRNPK protein. In vivo results further confirmed the tumor inhibitory effect of NJXA via the down-regulation of hnRNPK, and NJXA induced no apparent toxicity. Our study suggests that NJXA may be a novel anti-cancer drug candidate, especially for treating cancers with abnormally high hnRNPK expression.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital, Shanghai University of T.C.M, Shanghai 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China.
authors.forename: Jiling
authors.initials: J
authors.lastname: Feng
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Kong
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Xi
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China.
authors.forename: Baojun
authors.initials: B
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China.
authors.forename: Yuanzhi
authors.initials: Y
authors.lastname: Lao
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China. Electronic address: ths97029@163.com.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Tan
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital, Shanghai University of T.C.M, Shanghai 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China. Electronic address: xuhongxi88@gmail.com.
authors.forename: Hongxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D029760:Garcinia / Q000737:chemistry*; D006367:HeLa Cells; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D034622:RNA Interference; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D054875:Ubiquitination; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D044004:Xanthones / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D010936:Plant Extracts; D012261:Ribonucleoproteins; D044004:Xanthones; C000621544:nujiangexathone A; C072074:HNRNPK protein, human; D046988:Proteasome Endopeptidase Complex
keywords: Cell cycle; Cervical cancer; Garcinia species; Nujiangexathone A; hnRNPK