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Transcriptional regulation of G2/M regulatory proteins and perturbation of G2/M Cell cycle transition by a traditional Chinese medicine recipe.

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机构： [a]Chinese Medicine Anti-Cancer Evaluation Program, Greg Brown Laboratory, Central Clinical School and Charles Perkins Centre, The University of Sydney, Sydney,Australia [b]Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia [c]Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China [d]Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai,China [e]International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Schoolof Pharmacy, Jinan University, China [f]Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, China [g]School of Pharmacy, East China University of Science and Technology, China [h]VectorLAB, Department of Radiation Oncology, Chris O'Brien Lifehouse, Sydney, Australia [i]School of Physics, The University of Sydney, Sydney, Australia [j]Children's Cancer Institute Australia for Medical Research, Sydney, NSW, Australia [k]Centre for Childhood Cancer Research, UNSW Medicine, Sydney, Australia [l]School of Medicine, Western Sydney University, Australia [m]Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China [n]School of Science and Health, Western Sydney University, Australia

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关键词： G2 to M transition Prostate cancer Traditional Chinese medicine Hedyotis diffusa Willd Scutellaria barbata D Don

摘要：

Hedyotis diffusa Willd. (H) and Scutellaria barbata D.Don (S) are ancient anti-cancer Chinese herb medicines. When combined, known as HS, it is one of the most commonly prescribed Chinese Medicines for cancer patients today in China. 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. Effects of HS were analyzed in prostate cancer cell lines by evaluating proliferation, cell cycle profile, DNA damage and key regulators responsible for G2 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. HS treatment was observed to reduce DNA content and accumulated prostate cancer cells at the G2/M phase. Immunolabeling for phospho-Histone H3 in association with nocodazole to capture mitotic cells confirmed that HS impeded G2 to M transition. After excluding DNA damage-induced G2 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. HS acts by impeding the G2 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. Copyright © 2020 Elsevier B.V. All rights reserved.

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出版当年[2019]版：

大类 | 3 区医学

小类 | 2 区全科医学与补充医学 2 区植物科学 3 区药物化学 3 区药学

最新[2025]版：

大类 | 2 区医学

小类 | 1 区全科医学与补充医学 1 区药学 2 区药物化学 2 区植物科学

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第一作者机构： [a]Chinese Medicine Anti-Cancer Evaluation Program, Greg Brown Laboratory, Central Clinical School and Charles Perkins Centre, The University of Sydney, Sydney,Australia [b]Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia

通讯作者：

通讯机构： [a]Chinese Medicine Anti-Cancer Evaluation Program, Greg Brown Laboratory, Central Clinical School and Charles Perkins Centre, The University of Sydney, Sydney,Australia [b]Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia [m]Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China [n]School of Science and Health, Western Sydney University, Australia [*1]Chinese Medicine Anti-Cancer Evaluation Program, Greg Brown Laboratory, Central Clinical School and Charles Perkins Centre, The University of Sydney, Camperdown, NSW, 2006, Australia. [*2]Beijing University of Traditional Chinese Medicine, Beijing, 201203, China

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Transcriptional regulation of G2/M regulatory proteins and perturbation of G2/M Cell cycle transition by a traditional Chinese medicine recipe.

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