Thema: News: Synthetic chenodeoxycholic acid derivatives inhibit GBM
News: Synthetic chenodeoxycholic acid derivatives inhibit GBM
Anne[a]
17.09.2005 19:47:32
Int J Oncol. 2005 Sep;27(3):653-9
Synthetic chenodeoxycholic acid derivatives inhibit glioblastoma multiform tumor growth in vitro and in vivo.
Yee SB, Yeo WJ, Park BS, Kim JY, Baek SJ, Kim YC, Seo SY, Lee SH, Kim JH, Suh H, Kim ND, Lim YJ, Yoo YH.
Medical Science Research Center and College of Medicine (BK21 program), Dong-A University, Busan 602-714, South Korea.
We previously reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to explore whether synthetic CDCA derivatives, HS-1199 and HS-1200, had an anticancer effect on malignant glioblastoma cells. We administered them in culture to U-118MG, U-87MG, T98G, and U-373MG cells. The tested glioblastoma cells showed several lines of apoptotic manifestations, such as activation of caspase-3, degradation of DFF, production of poly(ADP-ribose) polymerase cleavage, nuclear condensation, inhibition of proteasome activity, reduction of mitochondrial membrane potential and the release of cytochrome c to cytosol and translocation of AIF to nuclei. Between the two synthetic derivatives, HS-1200 showed a stronger apoptosis-inducing effect than HS-1199. In vivo efficacy of HS-1200 was tested in U87MG cells inoculated into non-obese diabetic and severe combined immunodeficient (NOD/SCID) mice. The HS-1200 treatment significantly inhibited the increase of tumor size in NOD/SCID mice and prolonged the life spans. This study supports the possibility of synthetic CDCA derivatives as a potential chemotherapeutic agent.
Synthetic chenodeoxycholic acid derivatives inhibit glioblastoma multiform tumor growth in vitro and in vivo.
Yee SB, Yeo WJ, Park BS, Kim JY, Baek SJ, Kim YC, Seo SY, Lee SH, Kim JH, Suh H, Kim ND, Lim YJ, Yoo YH.
Medical Science Research Center and College of Medicine (BK21 program), Dong-A University, Busan 602-714, South Korea.
We previously reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to explore whether synthetic CDCA derivatives, HS-1199 and HS-1200, had an anticancer effect on malignant glioblastoma cells. We administered them in culture to U-118MG, U-87MG, T98G, and U-373MG cells. The tested glioblastoma cells showed several lines of apoptotic manifestations, such as activation of caspase-3, degradation of DFF, production of poly(ADP-ribose) polymerase cleavage, nuclear condensation, inhibition of proteasome activity, reduction of mitochondrial membrane potential and the release of cytochrome c to cytosol and translocation of AIF to nuclei. Between the two synthetic derivatives, HS-1200 showed a stronger apoptosis-inducing effect than HS-1199. In vivo efficacy of HS-1200 was tested in U87MG cells inoculated into non-obese diabetic and severe combined immunodeficient (NOD/SCID) mice. The HS-1200 treatment significantly inhibited the increase of tumor size in NOD/SCID mice and prolonged the life spans. This study supports the possibility of synthetic CDCA derivatives as a potential chemotherapeutic agent.
Anne[a]
