title: Patrinia scabiosaefolia induces mitochondrial-dependent apoptosis in a mouse model of colorectal cancer.
abstract: Disrupted apoptosis not only confers a survival advantage to cancer cells but also causes resistance to chemotherapies. Therefore, inducing cell apoptosis has become a promising strategy for anticancer treatment. Patrinia scabiosaefolia (PS) has long been used to clinically treat various types of malignancies including colorectal cancer (CRC). However, the precise mechanism of its tumoricidal activity remains largely unclear. Using a CRC mouse xenograft model and a human colon carcinoma cell line, HT-29, in the present study, we evaluated the antitumor activities of an ethanol extract of Patrinia scabiosaefolia (EEPS), and investigated the underlying molecular mechanisms. We found that EEPS inhibited CRC growth both in vivo and in vitro, without apparent adverse side-effects. Moreover, EEPS treatment promoted apoptosis in CRC tumor tissues and in HT-29 cells, suggesting that the inhibitory effect of EEPS on tumor growth was due to its pro-apoptotic activity. Furthermore, EEPS treatment inhibited the expression of anti-apoptotic Bcl-2 but enhanced pro-apoptotic Bax expression at both transcriptional and translational levels. Finally, EEPS induced the loss of mitochondrial membrane potential and activation of caspase-9 and -3 in HT-29 cells. Taken together, data in this study suggest that induction of cancer cell apoptosis via the mitochondrial-dependent pathway may be one of the mechanisms whereby PS exerts anticancer activity.
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Minhou Shangjie, Fuzhou, Fujian 350122, PR China.
authors.forename: Liya
authors.initials: L
authors.lastname: Liu
authors.forename: Aling
authors.initials: A
authors.lastname: Shen
authors.forename: Youqin
authors.initials: Y
authors.lastname: Chen
authors.forename: Lihui
authors.initials: L
authors.lastname: Wei
authors.forename: Jiumao
authors.initials: J
authors.lastname: Lin
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sferra
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Hong
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D053453:Caspase 9 / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics; D032405:Patrinia / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D014158:Transcription, Genetic; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9