Cytotoxic, apoptotic, and sensitization properties of ent-kaurane-type diterpenoids from Croton tonkinensis Gagnep on human liver cancer HepG2 and Hep3b cell lines

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 east...

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Published in:Fundamental & clinical pharmacology 2016-04, Vol.30 (2), p.137-146
Main Authors: Pham, Minh Quan, Iscache, Anne Laure, Pham, Quoc Long, Gairin, Jean Edouard
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
apoptosis
Apoptosis - drug effects
Carcinoma, Hepatocellular - drug therapy
Cell Line, Tumor
Croton - chemistry
cytotoxicity
Diterpenes - pharmacology
Diterpenes, Kaurane - chemistry
Diterpenes, Kaurane - pharmacology
ent-kaurane type diterpenoid
Hep G2 Cells
Hepatocellular carcinoma
HepG2 and Hep3b cell lines
Humans
Life Sciences
Liver Neoplasms - drug therapy
Plant Extracts - chemistry
Plant Extracts - pharmacology
sensitization
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Summary: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.
ISSN:0767-3981
1472-8206
DOI:10.1111/fcp.12176