title: Matrine‑induced apoptosis in Hep3B cells via the inhibition of MDM2.
abstract: Matrine, an alkaloid component derived from the Sophora root, can inhibit cancer cell proliferation and induce autophagy via p53 associated pathways. However, numerous tumor cells lack functional p53 and little is known about the effect of matrine on the p53‑deficient/mutant cancer cells. The present study aimed to assess anticancer effects of matrine in p53‑deficient human Hep3B hepatoma cells. The present results demonstrated that matrine caused Hep3B cell apoptosis by suppressing gene expression of minute double‑mutant (MDM)2. Notably, it was revealed that matrine inhibited MDM2 at the transcriptional level in a time‑ and dose‑dependent manner. This MDM2 inhibition resulted in induction of the p53 family member, p73; however, the functions of p73 were not induced since matrine‑induced p73 failed to activate its target genes, p21 and p53 upregulated modulator of apoptosis. The matrine‑induced downregulation of MDM2 led to an inhibition of inhibitor of apoptosis protein 3, which might serve a critical role in matrine‑induced apoptosis in MDM2‑overexpressing Hep3B cells. Finally, combination therapy of matrine with 100 µM epotoside successfully killed more Hep3B cells, suggesting that matrine can sensitize p53‑deficient Hep3B cells to epotoside‑induced apoptosis.
authors.affiliation: Department of Organ Transplantation and General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Organ Transplantation and General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jiequn
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Organ Transplantation and General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Organ Transplantation and General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Guangshun
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Organ Transplantation and General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Zhongqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Organ Transplantation and General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Zhongzhou
authors.initials: Z
authors.lastname: Si
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology*; D029909:Sophora / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D011807:Quinolizines; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2; D000093842:Matrines