Nayoung Kim1, Sang Hyub Lee2, Jun Hyuk Son3, Jae Min Lee4, Min-Jung Kang1, Bo Hye Kim1, Jung-Su Lee1, Ji Kon Ryu3, Yong-Tae Kim3. 1. Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 2. Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea gidoctor@snuh.org. 3. Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. 4. Department of Internal Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea.
Abstract
BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy with poor prognosis and limited therapeutic options. Effective prevention and treatment of CCA require developing novel anticancer agents and improved therapeutic regimens. As natural products are concidered a rich source of potential anticancer agents, we investigated the anticancer effect of fisetin in combination with gemcitabine. MATERIALS AND METHODS: Cytotoxic effect of fisetin and gemcitabine on a human CCA cell line SNU-308 was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis assay using propidium iodine and annexin V. Molecular mechanisms of fisetin action in CCA were investigated by western blotting. RESULTS: Fisetin was found to inhibit survival of CCA cells, through strongly phosphorylating ERK. It also induced cellular apoptosis additively in combination with gemcitabine. Expression of cellular proliferative markers, such as phospho-p65 and myelocytomatosis (MYC), were reduced by fisetin. CONCLUSION: These results suggest fisetin in combination with gemcitabine as a candidate for use in improved anticancer regimens. Copyright
BACKGROUND:Cholangiocarcinoma (CCA) is a malignancy with poor prognosis and limited therapeutic options. Effective prevention and treatment of CCA require developing novel anticancer agents and improved therapeutic regimens. As natural products are concidered a rich source of potential anticancer agents, we investigated the anticancer effect of fisetin in combination with gemcitabine. MATERIALS AND METHODS:Cytotoxic effect of fisetin and gemcitabine on a human CCA cell line SNU-308 was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis assay using propidium iodine and annexin V. Molecular mechanisms of fisetin action in CCA were investigated by western blotting. RESULTS:Fisetin was found to inhibit survival of CCA cells, through strongly phosphorylating ERK. It also induced cellular apoptosis additively in combination with gemcitabine. Expression of cellular proliferative markers, such as phospho-p65 and myelocytomatosis (MYC), were reduced by fisetin. CONCLUSION: These results suggest fisetin in combination with gemcitabine as a candidate for use in improved anticancer regimens. Copyright