文献类型：期刊文献

英文题名：Transcriptional regulation of G2/M regulatory proteins and perturbation of G2/M Cell cycle transition by a traditional Chinese medicine recipe

作者：Hnit, Su Su Thae[1,2,3];Yao, Mu[1,2,3];Xie, Chanlu[1,2,3];Ge, Guangbo[4];Bi, Ling[5];Jin, Shenyi[5];Jiao, Lijing[5];Xu, Ling[5];Long, Lina[6,7];Nie, Hong[6,7];Jin, Yu[8];Rogers, Linda[9,10];Suchowerska, Natalka[9,10];Wong, Matthew[11,12];Liu, Tao[11,12];De Souza, Paul[13];Li, Zhong[14];Dong, Qihan[1,2,3,15]

机构：[1]Univ Sydney, Cent Clin Sch, Greg Brown Lab, Chinese Med Anticanc Evaluat Program, Sydney, NSW, Australia;[2]Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia;[3]Royal Prince Alfred Hosp, Dept Endocrinol, Sydney, NSW, Australia;[4]Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai, Peoples R China;[5]Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western, Dept Oncol, Shanghai, Peoples R China;[6]Jinan Univ, Int Cooperat Lab Tradit Chinese Med Modernizat &, Chinese Minist Educ MOE, Sch Pharm, Guangzhou, Peoples R China;[7]Jinan Univ, Coll Pharm, Guangdong Prov Key Lab Pharmacodynam Constituents, Guangzhou, Peoples R China;[8]East China Univ Sci & Technol, Sch Pharm, Shanghai, Peoples R China;[9]Chris OBrien Lifehouse, Dept Radiat Oncol, VectorLAB, Sydney, NSW, Australia;[10]Univ Sydney, Sch Phys, Sydney, NSW, Australia;[11]Childrens Canc Inst Australia Med Res, Sydney, NSW, Australia;[12]UNSW Med, Ctr Childhood Canc Res, Sydney, NSW, Australia;[13]Western Sydney Univ, Sch Med, Sydney, NSW, Australia;[14]Beijing Univ Chinese Med, Dongzhimen Hosp, Beijing, Peoples R China;[15]Western Sydney Univ, Sch Sci & Hlth, Sydney, NSW, Australia

年份：2020

卷号：251

外文期刊名：JOURNAL OF ETHNOPHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000515196000016)】；

基金：This study was supported by Sydney Medical School Foundation grant (QD), Western Sydney University Partnership Grant (QD), Shanghai Municipal Health Commission: ZY(2018-2020)-CCCX-2004-09; Science and Technology Commission Shanghai Municipality: No. 16401970700; Shanghai Municipal Education Commission, "Gao Yuan Gao Feng" Team; Shanghai Municipal Health Commission: ZYKC201601020; Shanghai Sailing Program: No. 19YF1450000.

语种：英文

外文关键词：G(2) to M transition; Prostate cancer; Traditional Chinese medicine; Hedyotis diffusa Wilid.; Scutellaria barbata D.Don

摘要：Ethnopharmacological relevance: Hedyotis diffusa Willd. (H) and Scutellaria barbata D.Don (S) are ancient anticancer Chinese herb medicines. When combined, known as HS, it is one of the most commonly prescribed Chinese Medicines for cancer patients today in China. Aim of the study: The prevention of disease progression is a dominant concern for the growing number of men with prostate cancer. The purpose of this work is to evaluate the action and mode of action of Chinese Medicine recipe HS in inhibiting prostate cancer progression in preclinical models. Methods: Effects of HS were analyzed in prostate cancer cell lines by evaluating proliferation, cell cycle profile, DNA damage and key regulators responsible for G(2) to M phase transition. The transcriptional activities of these regulators were determined by RT-PCR and ChIP. The efficacy of HS in vitro was validated in an animal model. Results: HS treatment was observed to reduce DNA content and accumulated prostate cancer cells at the G(2)/M phase. Immunolabeling for phospho-Histone H3 in association with nocodazole to capture mitotic cells confirmed that HS impeded G(2) to M transition. After excluding DNA damage-induced G(2) arrest, it was revealed that HS reduced expression of Cyclin B1, CDK1, PLK1 and Aurora A at both protein and mRNA levels, with concomitant reduction of H3K4 tri-methylation at their promoter-regions. Animals that received oral administration of HS with a dosage relevant to clinical application showed reduced tumor volume and weight with a reduction of Cyclin B1, CDK1, PLK1 and Aurora A protein levels. Conclusions: HS acts by impeding the G(2) to M transition of prostate cancer cells. It is likely that the mode of action is transcriptionally suppressing proteins governing mitotic entry, without eliciting significant DNA damage.