Harmine induces anticancer activity in breast cancer cells via targeting TAZ. - GreenMedInfo Summary
Harmine induces anticancer activity in breast cancer cells via targeting TAZ.
Int J Oncol. 2019 Jun ;54(6):1995-2004. Epub 2019 Apr 9. PMID: 31081045
Harmine (HM) is aβ‑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.