Esculetin induces apoptosis of SMMC-7721 cells through IGF-1/PI3K/Akt-mediated mitochondrial pathways.
Esculetin (6,7-dihydroxycoumarin) is a coumarin derivative extracted from natural plants and has been reported to have anticancer activity. However, the mechanism by which esculetin prevents human hepatic cancer cell growth is still largely unknown. In this study, we investigated the effect of esculetin on human hepatocellular carcinoma (HCC) SMMC-7721 cells and explored the cell signal mechanism. Our data indicated that esculetin induced apoptosis in SMMC-7721 cells, which were supported by DAPI staining and Annexin V/PI staining. Meanwhile, esculetin increased the activities of caspase-3 and caspase-9, promoted bax expression, decreased bcl-2 expression, and triggered collapse of mitochondrial membrane potential, and increased cytochrome c release from mitochondria. In addition, the inactivation of IGF-1, PI3K, and Akt was observed after esculetin administration. Furthermore, pretreatment with IGF-1 before esculetin administration abrogated the pro-apoptotic effects of esculetin, while PI3K inhibitor increased the pro-apoptotic effects of esculetin. These results indicated that esculetin induced the apoptosis of SMMC-7721 cells through IGF-1/PI3K/Akt-regulated mitochondrial dysfunction.
a Department of Infectious Disease, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
Juan
J
Li
b Department of Anesthesiology, Taihe District Hospital of Jinzhou City, Jinzhou 121001, China.
Shuang
S
Li
a Department of Infectious Disease, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
Xiuli
X
Wang
c Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China.
Hongxin
H
Wang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014468:Umbelliferones / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014468:Umbelliferones; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C007628:esculetin
IGF-1; apoptose; apoptosis; cellules SMMC-7721 d’hépatome; esculetin; esculétine; hepatocellular carcinoma SMMC-7721 cells; mitochondria; mitochondrie