Harmine induces anticancer activity in breast cancer cells via targeting TAZ
Harmine induces anticancer activity in breast cancer cells via targeting TAZ
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DOI：
10.3892/ijo.2019.4777
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发表时间：
2019-06-01
影响因子：
5.2
通讯作者：
Peng, Caixia
中科院分区：
文献类型：
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作者：
Ding, Yu;He, Jinrong;Peng, Caixia
骆驼蓬碱（HM）是一种在多种药用植物中发现的β-咔啉生物碱。它已被用于民间医药的抗癌治疗，但HM对人类乳腺癌的分子机制仍不清楚。具有PDZ结合基序的转录辅激活因子（TAZ），也称为含WW结构域的转录调节因子1，在乳腺癌的发生和发展中起重要作用。本研究的目的是阐明HM在乳腺癌中的潜在抗癌活性和机制，在体外和体内。使用CCK-8测定法测量细胞增殖，通过流式细胞术和DAPI染色检测凋亡活性，并且使用伤口愈合测定法检查细胞迁移。Western blotting检测细胞外信号调节激酶（Erk）、磷酸化（p-）Erk、蛋白激酶B（Akt）、p-Akt、B细胞淋巴瘤2（Bcl-2）和Bcl-2相关X蛋白（Bax）的表达。采用逆转录-定量聚合酶链反应分析检测TAZ mRNA的表达。免疫组化法检测肿瘤组织中蛋白质的表达。HM在体外能显著抑制细胞增殖和迁移，促进细胞凋亡，在体内能显著抑制肿瘤生长。HM还能显著降低TAZ、p-Erk、p-Akt和Bcl-2的表达，而增加Bax的表达。TAZ在乳腺癌细胞中的过表达抑制HM的抗肿瘤作用。总之，发现HM诱导人乳腺癌细胞系的凋亡并阻止其增殖和迁移，可能通过下调TAZ。
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.