化学
细胞毒性
组蛋白脱乙酰基酶
自噬
PI3K/AKT/mTOR通路
癌症研究
细胞凋亡
肺癌
癌细胞
药理学
蛋白激酶B
伏立诺他
异羟肟酸
组蛋白脱乙酰酶抑制剂
癌症
细胞生长
生物化学
生物
组蛋白
体外
立体化学
医学
肿瘤科
内科学
基因
作者
Nilkamal H. Karelia,Dhimant Desai,Jeremy A. Hengst,Shantu Amin,Sairam Rudrabhatla,Jong K. Yun
标识
DOI:10.1016/j.bmcl.2010.08.113
摘要
Cancer therapy has moved beyond conventional chemotherapeutics to more mechanism-based targeted approaches. Studies demonstrate that histone deacetylase (HDAC) is a promising target for anticancer agents. Numerous, structurally diverse, hydroxamic acid derivative, HDAC inhibitors have been reported and have been shown to induce growth arrest, differentiation, autophagy, and/or apoptotic cell death by inhibiting multiple signaling pathways in cancer cells. Suberoylanilide hydroxamic acid (SAHA) has emerged as an effective anticancer therapeutic agent and was recently approved by the FDA for the treatment of advanced cutaneous T-cell lymphoma. In our previous study, we reported the development of the novel, potent, selenium-containing HDAC inhibitors (SelSA-1 and SelSA-2). In this study, the effects of SelSA-1 and SelSA-2 on signaling pathways and cytotoxicity were compared with the known HDAC inhibitor, SAHA, in lung cancer cell lines. After 24 h of treatment, SelSA-1 and SelSA-2 inhibited lung cancer cell growth to a greater extent than SAHA in a dose-dependent manner with IC50 values at low micromolar concentrations. SelSA-1 and SelSA-2 inhibited ERK and PI3K-AKT signaling pathways while simultaneously increasing in autophagy in A549 cells in a time dependent manner. This preliminary study demonstrates the effectiveness of the selenium-containing analogs of SAHA, SelSA-1, and SelSA-2, as HDAC inhibitors and provides insight into the improvement and/or development of these analogs as a therapeutic approach for the treatment of lung cancer.
科研通智能强力驱动
Strongly Powered by AbleSci AI