Detailed Abstract
[E-poster]
[EP058] Application of self-assembly peptides targeting the mitochondria as a novel treatment for sorafenib-resistant hepatocellular carcinoma cells
Tae Ho HONG1, Ho Joong CHOI1, Jung Hyun PARK2, Kee-Hwan KIM3, Dong Do YOU5, Jae Hyun HAN5, Kwang Yeol PAIK4, Say-June KIM*1
1Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Korea
2Department of Surgery, Eunpeong St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Korea
3Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Korea
4Department of Surgery, Yeouido ST. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Korea
5Department of Surgery, St. Paul's Hospital, College of Medicine, the Catholic University of Korea, Korea
Introduction : Currently, there is no appropriate treatment option for patients with sorafenib-resistant hepatocellular carcinoma (HCC). Meanwhile, pronounced anticancer activities of newly-developed mitochondria-accumulating self-assembly peptides (Mito-FF) have been demonstrated. This study intended to determine the anticancer effects of Mito-FF against sorafenib-resistant HCC cells.
Methods : To generate sorafenib-resistant cultures, Huh7 HCC cells were grown in vitro using increasing doses of sorafenib (0.5 µmol/L initially and increasing up to 15 µmol/L) for a total of 8 months. Anticancer effects of Mito-FF against sorafenib-resistant Huh7 (Huh7-R) cells were determined using flow cytometry, cell viability testing, western blot analysis, and MitoSOX staining.
Results : Mito-FF led to the significant reduction of cell viability as well as the increase of apoptosis in Huh7-R cells. Relatively higher populations of apoptotic cell populations were observed in Huh7-R cells following Mito-FF treatment compared to sorafenib (P<0.05). Compared to sorafenib, Mito-FF led to the generation of relatively higher amounts of mitochondrial ROS as well as the greater reduction in the expression of antioxidant enzymes (P<0.05). Addition of an ROS inhibitor (N-acetyl-L-cysteine) significantly reduced the expression of poly-ADP ribose polymerase (an apoptotic marker) in the Mito-FF treated Huh7-R cells (P<0.05).
Conclusions : Mito-FF was found to significantly promote cell apoptosis while inhibiting cell proliferation of Huh7-R cells. Mito-FF also reduces the expression of antioxidant enzymes while significantly increasing mitochondrial ROS in Huh7-R cells. The pro-apoptotic effect of Mito-FFs for Huh7-R cells is possibly caused by their up-regulation of mitochondrial ROS, which is caused by the destruction of the mitochondria of HCC cells.
Methods : To generate sorafenib-resistant cultures, Huh7 HCC cells were grown in vitro using increasing doses of sorafenib (0.5 µmol/L initially and increasing up to 15 µmol/L) for a total of 8 months. Anticancer effects of Mito-FF against sorafenib-resistant Huh7 (Huh7-R) cells were determined using flow cytometry, cell viability testing, western blot analysis, and MitoSOX staining.
Results : Mito-FF led to the significant reduction of cell viability as well as the increase of apoptosis in Huh7-R cells. Relatively higher populations of apoptotic cell populations were observed in Huh7-R cells following Mito-FF treatment compared to sorafenib (P<0.05). Compared to sorafenib, Mito-FF led to the generation of relatively higher amounts of mitochondrial ROS as well as the greater reduction in the expression of antioxidant enzymes (P<0.05). Addition of an ROS inhibitor (N-acetyl-L-cysteine) significantly reduced the expression of poly-ADP ribose polymerase (an apoptotic marker) in the Mito-FF treated Huh7-R cells (P<0.05).
Conclusions : Mito-FF was found to significantly promote cell apoptosis while inhibiting cell proliferation of Huh7-R cells. Mito-FF also reduces the expression of antioxidant enzymes while significantly increasing mitochondrial ROS in Huh7-R cells. The pro-apoptotic effect of Mito-FFs for Huh7-R cells is possibly caused by their up-regulation of mitochondrial ROS, which is caused by the destruction of the mitochondria of HCC cells.
SESSION
E-poster
E-Session 7/27 ~ 7/29 ALL DAY