title: Growth inhibition by pennogenyl saponins from Rhizoma paridis on hepatoma xenografts in nude mice.
abstract: Rhizoma paridis is widely used in the traditional Chinese medicine for the treatment of cancers. Steroidal saponins, including diosgenyl saponins and the characterized component pennogenyl saponins, are regarded as the main active components of R. paridis. To date, quite a bit of research has been published which attempt to explore the in vivo anticancer effects and the underlying mechanisms of pennogenyl saponins, compounds which are present at quite low levels in the plant. In the present study, two known pennogenyl saponins (PS1 and PS2) were isolated from R. paridis axialis and identified by spectral techniques. The anti-cancer activity of these two pennogenyl saponins was investigated in nude mice bearing human hepatocellular carcinoma (HCC) HepG2 xenografts. PS1 or PS2 (purity >98%, 1 or 3mg/kg) was administered by intraperitoneal injection, respectively. The specimens of HepG2 xenografts were removed for mechanistic study. The current results indicated that both PS1 and PS2 dose-dependently prevented the growth of HepG2 xenografts. Western blotting analysis showed that the anticancer effects of these two monomers were associated with apoptosis induction and proliferation inhibition through activation of both caspase-dependent and caspase-independent apoptotic pathways, regulation of mitogen-related protein kinase pathway and inhibition of PI3K/Akt pathway. The present data suggest, for the first time, that PS1 and PS2 effectively inhibit human HCC progression through regulation of the signal pathways associated with apoptosis and proliferation, and have the potential for the treatment of HCC.
authors: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education, West China School of Pharmacy, and Translational Neuroscience Center, Sichuan University, Chengdu, China.
authors: Ya-Shu
authors: YS
authors: Chen
authors: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education, West China School of Pharmacy, and Translational Neuroscience Center, Sichuan University, Chengdu, China.
authors: Yao
authors: Y
authors: He
authors: Department of Pharmacognosy, Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China; Sichuan Academy of Chinese Medicine Sciences, Chengdu, China.
authors: Chu
authors: C
authors: Chen
authors: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education, West China School of Pharmacy, and Translational Neuroscience Center, Sichuan University, Chengdu, China.
authors: Yi
authors: Y
authors: Zeng
authors: Sichuan Academy of Chinese Medicine Sciences, Chengdu, China.
authors: Dan
authors: D
authors: Xue
authors: Sichuan Academy of Chinese Medicine Sciences, Chengdu, China.
authors: Fei-Yan
authors: FY
authors: Wen
authors: Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, WI 53226, USA.
authors: Ling
authors: L
authors: Wang
authors: Department of Pharmacognosy, Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors: Hao
authors: H
authors: Zhang
authors: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education, West China School of Pharmacy, and Translational Neuroscience Center, Sichuan University, Chengdu, China. Electronic address: dujr07@gmail.com.
authors: Jun-Rong
authors: JR
authors: Du
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D004365:Drugs, Chinese Herbal; D012503:Saponins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases
keywords: Anticancer activity; Hepatocellular carcinoma; Nude mice; Pennogenyl saponins; Rhizoma paridis axialis