title: In vitro and in vivo antitumor activities of tenacissoside C from Marsdenia tenacissima.
abstract: Tenacissoside C, a natural bioactive compound of C21 steroidal saponins, was isolated and purified from air-dried stems of Marsdenia tenacissima. In the present study, the MTT assay showed that tenacissoside C exhibited obvious cytotoxicity in K562 cells with IC50 values of 31.4, 22.2, and 15.1 µM for 24, 48, and 72 h, respectively. Flow cytometry analysis indicated that the antiproliferative activity induced by tenacissoside C might be executed via G0/G1 cell cycle arrest and proapoptosis in K562 cells. Western blotting analysis elucidated that: A) Tenacissoside C induced K562 cell cycle (G0/G1) arrest via downregulating cycline D1 protein expression; and B) Tenacissoside C induced K562 cell apoptosis via the mitochondrial pathway by downregulating Bcl-2 and Bcl-xL protein expression, upregulating Bax and Bak protein expression, and activating caspase-9 and caspase-3. In vivo, significant tumor growth inhibition activity of tenacissoside C was observed in K562 cell-bearing nude mice, accompanied by a significant antiangiogenic effect in vivo against K562 cells (a marked decrease in MVD) and associated with enhanced apoptotic cell death (TUNEL staining assay in vivo), both in dose-dependent manners. The treatment with tenacissoside C did not significantly affect body mass and macroscopic examination of the organs in this mouse tumor model.
authors: Department of Hematology & State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Bengui
authors: B
authors: Ye
authors: Department of Hematology & State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Jinrong
authors: J
authors: Yang
authors: Department of Hematology & State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Jun
authors: J
authors: Li
authors: Department of Hematology & State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Ting
authors: T
authors: Niu
authors: Department of Medicinal Natural Products, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
authors: Shu
authors: S
authors: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells / Q000187:drug effects; D031101:Marsdenia / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D010840:Phytosterols / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; C530104:CCND1 protein, human; D010840:Phytosterols; D012503:Saponins; D051020:bcl-X Protein; C000592517:tenacissoside C; D019938:Cyclin D1; D053148:Caspase 3; D053453:Caspase 9