title: Ligustrum lucidum Ait. fruit extract induces apoptosis and cell senescence in human hepatocellular carcinoma cells through upregulation of p21.
abstract: Nü-zhen-zi, the fruit of Ligustrum lucidum Ait., is one of the most frequently used liver Yin tonifying Chinese herbs for the treatment of liver cancer. However, the effect of Ligustrum lucidum fruit on hepatocarcinoma cells remains unknown. In the present study, we evaluated the effects of a Ligustrum lucidum fruit extract (LLFE) on human hepatocellular carcinoma Bel-7402 cells. The results showed that LLFE inhibited the proliferation of the Bel-7402 cells in a dose- and time-dependent manner. LLFE induced apoptosis in Bel-7402 cells accompanied by activation of caspase-3, -8 and -9. LLFE-induced apoptosis was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. LLFE treatment also caused a large and flat morphologic cellular change, positive SA-β-gal staining, and G0/G1 phase cell cycle arrest in the Bel-7402 cells, accompanied by upregulation of p21 and downregulation of RB phosphorylation. Specific knockdown of p21 expression by RNA interference partially abrogated LLFE-induced apoptosis, and significantly abrogated LLFE-induced cell senescence. These observations suggest that Nü-zhen-zi is a potential anticancer herb and support the traditional use of Nü-zhen-zi for hepatocarcinoma treatment.
authors.affiliation: Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Deng
authors.affiliation: Department of Science and Technology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: An
authors.affiliation: Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, P.R. China.
authors.forename: Chuan-Fang
authors.initials: CF
authors.lastname: Pan
authors.affiliation: Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, P.R. China.
authors.forename: Ke-Ping
authors.initials: KP
authors.lastname: Shen
authors.affiliation: Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, P.R. China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Wei
authors.affiliation: Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, P.R. China.
authors.forename: Shuang-Shuang
authors.initials: SS
authors.lastname: Wang
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D006801:Humans; D031659:Ligustrum / Q000737:chemistry*; D008113:Liver Neoplasms / Q000235:genetics*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D061945:Caspase Inhibitors; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010936:Plant Extracts; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases