Songzhe Piao1, Minyong Kang2, Young Ju Lee2, Woo Suk Choi3, Yang-Sook Chun4, Cheol Kwak2, Hyeon Hoe Kim5. 1. Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Urology, Yanbian University Hospital, Yanji, Jilin Province, China. 2. Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea. 3. Department of Urology, Konkuk University Hospital, Seoul, Republic of Korea. 4. Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. 5. Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: hhkim@snu.ac.kr.
Abstract
OBJECTIVE: To evaluate the in vitro and in vivo effects of escin on human castration-resistant prostate cancer (CRPC) cells, PC-3 and DU-145. MATERIALS AND METHODS: The inhibition of cell proliferation and its mechanism were assessed through a cytotoxicity assay, flow cytometry, and Western blot. The in vivo efficacy of escin in CRPC cells was assessed using a xenograft tumor model subcutaneously established in BALB/c nude mice. RESULTS: The treatment with escin significantly reduced cell viability of CRPC cells in a dose- and time-dependent manner. Escin induced apoptosis in a time-dependent manner, which was accompanied by increases in pro-apoptotic (BCL-2 associated X protein, cleaved-caspase3, and cleaved-poly [adenosine diphosphate-ribose] polymerase) proteins and decreases in antiapoptotic (X-linked inhibitor of apoptosis protein, cellular inhibitor of apoptosis protein-1, cellular inhibitor of apoptosis protein-2B-cell leukemia/lymphoma-2, and B-cell lymphoma-extra large) proteins. Escin induced G2/M-phase cell cycle arrest and thus led to a significant decrease in the expression of cyclinB1 and its activating partner cyclin-dependent kinase 1, with the concomitant induction of p21. In addition, escin significantly inhibited the growth of CRPC cells in xenograft models. CONCLUSION: The results show that escin induced cytotoxic effects on CRPC cells through the induction of apoptosis and G2/M cell cycle arrest, indicating it may be a novel therapeutic agent for CRPC.
OBJECTIVE: To evaluate the in vitro and in vivo effects of escin on human castration-resistant prostate cancer (CRPC) cells, PC-3 and DU-145. MATERIALS AND METHODS: The inhibition of cell proliferation and its mechanism were assessed through a cytotoxicity assay, flow cytometry, and Western blot. The in vivo efficacy of escin in CRPC cells was assessed using a xenograft tumor model subcutaneously established in BALB/c nude mice. RESULTS: The treatment with escin significantly reduced cell viability of CRPC cells in a dose- and time-dependent manner. Escin induced apoptosis in a time-dependent manner, which was accompanied by increases in pro-apoptotic (BCL-2 associated X protein, cleaved-caspase3, and cleaved-poly [adenosine diphosphate-ribose] polymerase) proteins and decreases in antiapoptotic (X-linked inhibitor of apoptosis protein, cellular inhibitor of apoptosis protein-1, cellular inhibitor of apoptosis protein-2B-cell leukemia/lymphoma-2, and B-cell lymphoma-extra large) proteins. Escin induced G2/M-phase cell cycle arrest and thus led to a significant decrease in the expression of cyclinB1 and its activating partner cyclin-dependent kinase 1, with the concomitant induction of p21. In addition, escin significantly inhibited the growth of CRPC cells in xenograft models. CONCLUSION: The results show that escin induced cytotoxic effects on CRPC cells through the induction of apoptosis and G2/M cell cycle arrest, indicating it may be a novel therapeutic agent for CRPC.
Authors: Lenka Varinská; Lenka Fáber; Martin Kello; Eva Petrovová; Ľudmila Balážová; Peter Solár; Matúš Čoma; Peter Urdzík; Ján Mojžiš; Emil Švajdlenka; Pavel Mučaji; Peter Gál Journal: Molecules Date: 2018-01-17 Impact factor: 4.411