Anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma.
BACKGROUND
The aim of this study is to investigate the anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma.


METHODS
The anticancer activity of streptochlorin was evaluated in vitro in various cholangiocarcinoma cell lines for apoptosis, proliferation, invasiveness, and expression of various protein levels. A liver metastasis model was prepared by splenic injection of HuCC-T1 cholangiocarcinoma cells using a BALB/c nude mouse model to study the systemic antimetastatic efficacy of streptochlorin 5 mg/kg at 8 weeks. The antitumor efficacy of subcutaneously injected streptochlorin was also assessed using a solid tumor xenograft model of SNU478 cells for 22 days in the BALB/c nude mouse.


RESULTS
Streptochlorin inhibited growth and secretion of vascular endothelial growth factor by cholangiocarcinoma cells in a dose-dependent manner and induced apoptosis in vitro. In addition, streptochlorin effectively inhibited invasion and migration of cholangiocarcinoma cells. Secretion of vascular endothelial growth factor and activity of matrix metalloproteinase-9 in cholangiocarcinoma cells were also suppressed by treatment with streptochlorin. Streptochlorin effectively regulated metastasis of HuCC-T1 cells in a mouse model of liver metastasis. In a tumor xenograft study using SNU478 cells, streptochlorin significantly inhibited tumor growth without changes in body weight when compared with the control.


CONCLUSIONS
These results reveal that streptochlorin is a promising chemotherapeutic agent to the treatment of cholangiocarcinoma.
Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
Tae Won
TW
Kwak
Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, Republic of Korea.
Hee Jae
HJ
Shin
Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
Young-Il
YI
Jeong
Department of Anatomy, School of Medicine, Pusan National University, Gyeongnam, Republic of Korea.
Myoung-Eun
ME
Han
Department of Anatomy, School of Medicine, Pusan National University, Gyeongnam, Republic of Korea.
Sae-Ock
SO
Oh
Genewel Co Ltd. Gyeonggi-do, Pusan National University, Yangsan, Gyeongnam, Republic of Korea.
Hyun-Jung
HJ
Kim
School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea.
Do Hyung
DH
Kim
Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
Dae Hwan
DH
Kang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010080:Oxazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D007211:Indoles; D009363:Neoplasm Proteins; D010080:Oxazoles; C526070:streptochlorin; D053148:Caspase 3
chemotherapeutic agent; cholangiocarcinoma; invasion; metastasis; streptochlorin