title: Chinese Herbal Mixture, Tien-Hsien Liquid, Induces G2/M Cycle Arrest and Radiosensitivity in MCF-7 Human Breast Cancer Cells through Mechanisms Involving DNMT1 and Rad51 Downregulation.
abstract: The Chinese herbal mixture, Tien-Hsien Liquid (THL), has been proven to suppress the growth and invasiveness of cancer cells and is currently regarded as a complementary medicine for the treatment of cancer. Our previous study using acute promyelocytic leukemia cells uncovered its effect on the downregulation of DNA methyltransferase 1 (DNMT1) which is often overexpressed in cancer cells resulting in the repression of tumor suppressors via hypermethylation. Herein, we explored the effects of THL in MCF-7 breast cancer cells that also demonstrate elevated DNMT1. The results show that THL dose-dependently downregulated DNMT1 accompanied by the induction of tumor suppressors such as p21 and p15. THL arrested cell cycle in G2/M phase and decreased the protein levels of cyclin A, cyclin B1, phospho-pRb, and AKT. DNMT1 inhibition was previously reported to exert a radiosensitizing effect in cancer cells through the repression of DNA repair. We found that THL enhanced radiation-induced clonogenic cell death in MCF-7 cells and decreased the level of DNA double-strand break repair protein, Rad51. Our observations may be the result of DNMT1 downregulation. Due to the fact that DNMT1 inhibition is now a mainstream strategy for anticancer therapy, further clinical trials of THL to confirm its clinical efficacy are warranted.
authors.affiliation: Comprehensive Cancer Center, Taipei Medical University, Taipei 11031, Taiwan; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Chih-Jung
authors.identifier: 0000-0001-6072-4033
authors.initials: CJ
authors.lastname: Yao
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Jyh-Ming
authors.initials: JM
authors.lastname: Chow
authors.affiliation: Formosa Cancer Foundation, Taipei 10597, Taiwan.
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Yang
authors.affiliation: Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Hui-Ching
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Chia-Lun
authors.initials: CL
authors.lastname: Chang
authors.affiliation: The Ph.D. Program for Translational Medicine, Taipei Medical University-Academia Sinica, Taipei 11031, Taiwan.
authors.forename: Hsin-Lun
authors.initials: HL
authors.lastname: Lee
authors.affiliation: Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Lai
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli County 35053, Taiwan.
authors.forename: Shuang-En
authors.initials: SE
authors.lastname: Chuang
authors.affiliation: Comprehensive Cancer Center, Taipei Medical University, Taipei 11031, Taiwan; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli County 35053, Taiwan.
authors.forename: Gi-Ming
authors.identifier: 0000-0001-6123-8870
authors.initials: GM
authors.lastname: Lai