Rai Reeta, Dutta Roshan Kumar, Singh Surjeet, Yadav Dharmendra Kumar, Kumari Seema, Singh Harpreet, Gupta Rinkoo Devi, Pratap Ramendra
Department of Biochemistry, AIIMS, Ansari Nagar, New Delhi 110029, India.
Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi 110021, India.
Bioorg Med Chem Lett. 2018 May 15;28(9):1574-1580. doi: 10.1016/j.bmcl.2018.03.057. Epub 2018 Mar 22.
A series of functionalized naphthalene was synthesized and screened against human prostate cancer cell line (PC-3). The in vitro antiproliferative activity of the synthesized compounds was evaluated by monitoring their cytotoxic effects against PC-3 cells by using MTT assay. We observed that compound 5f resulted in more than 50% cell death at 14 µM. Treatment of PC-3 cells with 5f provides apoptosis by flow cytometry. Western blotting showed decreased expression of pro-caspase 8 and 9. Our study shows that cancer cell treated with 5f has higher concentration of reactive oxygen species as compare to untreated sample, which facilitate cancerous cell to enter apoptosis. Exact mechanism by which ROS is generated after 5f treatment is still under study. Molecular docking study further strengthens the results obtained from in vitro experiments. Compound 5f can be considered as a promising leads for anticancer agent against prostate cancer cells due to its potent cytotoxic activity and apoptotic effect.
合成了一系列功能化萘，并针对人前列腺癌细胞系（PC-3）进行筛选。通过MTT法监测合成化合物对PC-3细胞的细胞毒性作用，评估其体外抗增殖活性。我们观察到化合物5f在14µM时导致超过50%的细胞死亡。用5f处理PC-3细胞通过流式细胞术诱导凋亡。蛋白质印迹显示前半胱天冬酶8和9的表达降低。我们的研究表明，与未处理的样品相比，用5f处理的癌细胞具有更高浓度的活性氧，这促使癌细胞进入凋亡。5f处理后产生活性氧的确切机制仍在研究中。分子对接研究进一步强化了体外实验获得的结果。由于其强大的细胞毒性活性和凋亡作用，化合物5f可被视为一种有前景的抗前列腺癌细胞抗癌剂先导物。
