title: Cytotoxic, apoptotic, and sensitization properties of ent-kaurane-type diterpenoids from Croton tonkinensis Gagnep on human liver cancer HepG2 and Hep3b cell lines.
abstract: Human hepatocellular carcinoma (HCC) is the most common type of liver cancer, the second most common cause of death from cancer worldwide. A very poor prognosis and a lack of effective treatments make liver cancer a major public health problem, notably in less developed regions, particularly in eastern Asia. This fully justifies the search of new molecules and therapeutic strategies against HCC. Ent-kaurane diterpenoids are natural compounds displaying a broad spectrum of potential therapeutic effects including anticancer activity. In this study, we analyzed the pharmacological properties of a family of ent-kaurane diterpenoids from Croton tonkinensis Gagnep in human HepG2 and Hep3b cell lines, used as cellular reference models for in vitro evaluation of new molecules active on HCC. A structure-related cytotoxicity was observed against both HCC cell lines, enlighting the role of the 16-en-15-one skeleton of ent-kaurane diterpenoids. Cytotoxicity was closely correlated to apoptosis, evidenced by concentration-dependent subG1 cell accumulation, and increased annexin V expression. In addition, subtoxic concentration of ent-kaurane diterpenoid dramatically enhanced the sensitivity of HCC cells to doxorubicin. All together, our data bring strong support to the potential interest of ent-kaurane diterpenoids, alone or in combination with a cytotoxic agent, in cancer and more precisely against HCC.
authors.affiliation: Faculté des Sciences Pharmaceutiques, UPS, UMR 152 Pharma-DEV, Université de Toulouse, Université Toulouse 3, 35 Chemin des Maraîchers, Toulouse Cedex 9, F-31062, France.|Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Building 1H, 18 Hoang Quoc Viet, Hanoi, Vietnam.
authors.forename: Minh Quan
authors.initials: MQ
authors.lastname: Pham
authors.affiliation: Plateau technique de cytométrie et tri cellulaire, UMR INSERM 1043-CNRS 5282- Université Toulouse 3, CHU Purpan, BP3028, 31024, Toulouse Cedex 3, France.
authors.forename: Anne Laure
authors.initials: AL
authors.lastname: Iscache
authors.affiliation: Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Building 1H, 18 Hoang Quoc Viet, Hanoi, Vietnam.
authors.forename: Quoc Long
authors.initials: QL
authors.lastname: Pham
authors.affiliation: Faculté des Sciences Pharmaceutiques, UPS, UMR 152 Pharma-DEV, Université de Toulouse, Université Toulouse 3, 35 Chemin des Maraîchers, Toulouse Cedex 9, F-31062, France.
authors.forename: Jean Edouard
authors.initials: JE
authors.lastname: Gairin
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D029802:Croton / Q000737:chemistry*; D004224:Diterpenes / Q000494:pharmacology*; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D045786:Diterpenes, Kaurane; D010936:Plant Extracts
keywords: HepG2 and Hep3b cell lines; Hepatocellular carcinoma; apoptosis; cytotoxicity; ent-kaurane type diterpenoid; sensitization