PMID- 31081045 OWN - NLM STAT- MEDLINE DCOM- 20190830 LR - 20211204 IS - 1791-2423 (Electronic) IS - 1019-6439 (Print) IS - 1019-6439 (Linking) VI - 54 IP - 6 DP - 2019 Jun TI - Harmine induces anticancer activity in breast cancer cells via targeting TAZ. PG - 1995-2004 LID - 10.3892/ijo.2019.4777 [doi] AB - Harmine (HM) is a beta‑carboline alkaloid found in multiple medicinal plants. It has been used in folk medicine for anticancer therapy; however, the molecular mechanism of HM on human breast cancer remains unclear. Transcriptional co‑activator with PDZ‑binding motif (TAZ), also known as WW domain‑containing transcription regulator 1, serves an important role in the carcinogenesis and progression of breast cancer. The aim of the present study was to elucidate the potential anticancer activity and mechanism of HM in breast cancer, in vitro and in vivo. Cell proliferation was measured using a CCK‑8 assay, apoptotic activity was detected by flow cytometry and DAPI staining, and cell migration was examined using a wound healing assay. The expression of proteins, including extracellular signal‑regulate kinase (Erk), phosphorylated (p‑) Erk, protein kinase B (Akt), p‑Akt, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax), were determined by western blotting. The mRNA expression of TAZ was detected using reverse transcription‑quantitative polymerase chain reaction analysis. The expression of proteins in mouse tumor tissues were examined by immunohistochemistry. HM significantly suppressed cellular proliferation and migration, promoted apoptosis in vitro and inhibited tumor growth in vivo. In addition, HM significantly decreased the expression of TAZ, p‑Erk, p‑Akt and Bcl‑2, but increased that of Bax. The overexpression of TAZ in breast cancer cells inhibited the antitumor effect of HM. In conclusion, HM was found to induce apoptosis and prevent the proliferation and migration of human breast cancer cell lines, possibly via the downregulation of TAZ. FAU - Ding, Yu AU - Ding Y AD - Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China. FAU - He, Jinrong AU - He J AD - Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China. FAU - Huang, Juan AU - Huang J AD - Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China. FAU - Yu, Tong AU - Yu T AD - Department of Traditional Chinese Medicine, Humanwell Healthcare (Group) Co., Ltd., Wuhan, Hubei 430075, P.R. China. FAU - Shi, Xiaoyan AU - Shi X AD - Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China. FAU - Zhang, Tianzhu AU - Zhang T AD - Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China. FAU - Yan, Ge AU - Yan G AD - Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China. FAU - Chen, Shanshan AU - Chen S AD - Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China. FAU - Peng, Caixia AU - Peng C AD - Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China. LA - eng PT - Journal Article DEP - 20190409 PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 0 (Transcriptional Coactivator with PDZ-Binding Motif Proteins) RN - 0 (WWTR1 protein, human) RN - 4FHH5G48T7 (Harmine) SB - IM MH - Antineoplastic Agents, Phytogenic/*administration & dosage/pharmacology MH - Breast Neoplasms/*drug therapy/genetics/metabolism MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Female MH - Gene Expression Regulation, Neoplastic/drug effects MH - Harmine/*administration & dosage/pharmacology MH - Humans MH - Intracellular Signaling Peptides and Proteins/genetics/*metabolism MH - MCF-7 Cells MH - Signal Transduction/drug effects MH - Trans-Activators MH - Transcription Factors MH - Transcriptional Coactivator with PDZ-Binding Motif Proteins MH - Xenograft Model Antitumor Assays PMC - PMC6521938 EDAT- 2019/05/14 06:00 MHDA- 2019/08/31 06:00 PMCR- 2019/04/09 CRDT- 2019/05/14 06:00 PHST- 2018/10/26 00:00 [received] PHST- 2019/03/27 00:00 [accepted] PHST- 2019/05/14 06:00 [entrez] PHST- 2019/05/14 06:00 [pubmed] PHST- 2019/08/31 06:00 [medline] PHST- 2019/04/09 00:00 [pmc-release] AID - ijo-54-06-1995 [pii] AID - 10.3892/ijo.2019.4777 [doi] PST - ppublish SO - Int J Oncol. 2019 Jun;54(6):1995-2004. doi: 10.3892/ijo.2019.4777. Epub 2019 Apr 9.