title: The anti-lung cancer activities of steroidal saponins of P. polyphylla Smith var. chinensis (Franch.) Hara through enhanced immunostimulation in experimental Lewis tumor-bearing C57BL/6 mice and induction of apoptosis in the A549 cell line.
abstract: P. polyphylla Smith var. chinensis (Franch.) Hara (PPSCFH) has been used as medicinal Paris for the prevention and treatment of cancers in China for thousands of years. Its main components, steroidal saponins (PRS), have been confirmed to inhibit tumor growth. In the present study, the immunostimulation of PRS was investigated in Lewis bearing-C57BL/6 mice while the induction of apoptosis in A549 cells was also studied. The treatment with PRS (2.5, 5.0 and 7.5 mg/kg) significantly inhibited tumor, volume, and weight in the C57BL/6 mice. The rates of inhibition of PRS (at 2.5, 5.0 and 7.5 mg/kg) were 26.49 ± 17.30%, 40.32 ± 18.91% and 54.94 ± 16.48%, respectively. The spleen and thymus indexes were increased remarkably, while the levels of inflammatory cytokines including TNF-α, IL-8 and IL-10 in serum were decreased according to ELISA assays. For A549 cells, Hoechst 33342 staining and annexin V/PI by flow cytometry showed that PRS (0.25, 0.50 and 0.75 mg/mL) induced nuclear changes of A549 cells with DNA condensation and fragmentations of chromatin, as well as inducing apoptosis. Furthermore, PRS could also attenuate the over-generation of intracellular ROS. Western blotting analysis showed a significant decrease on the expressions of proinflammatory cytokines MCP-1, IL-6 and TGF-β1, as well as cell adhesion molecule ICAM-1, by treatment with PRS. Our results demonstrated that the inhibition of PRS on tumor growth might be associated with the amelioration of inflammation responses, induction of apoptosis, as well as the decrease of ROS. These results suggested that PRS implied a potential therapeutic effect in the lung cancer treatment.
authors.affiliation: Department of Oncology, the Affiliated Hospital of Nanjing University of Chinese Medicine, No.155, Hanzhong Road, Nanjing 210029, Jiangsu, China. wenmoxiushi@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Jun-Fei
authors.initials: JF
authors.lastname: Gu
authors.forename: Xi
authors.initials: X
authors.lastname: Zou
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.forename: Dong
authors.initials: D
authors.lastname: Qin
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Zhou
authors.forename: Bao-Xin-Zi
authors.initials: BX
authors.lastname: Liu
authors.forename: Yun-Tao
authors.initials: YT
authors.lastname: Zhu
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Jia
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.forename: Rui-Ping
authors.initials: RP
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D007155:Immunologic Factors; D017382:Reactive Oxygen Species; D012503:Saponins