title: Paris saponin VII from trillium tschonoskii reverses multidrug resistance of adriamycin-resistant MCF-7/ADR cells via P-glycoprotein inhibition and apoptosis augmentation.
abstract: BACKGROUND
  Saponins of several herbs are known to induce apoptosis in some cancer cells and are proposed to be promising modulators of drug resistance. In the present study, we extracted Paris saponin VII (PS VII), a kind of saponin, from Trillium tschonoskii Maxim. and observed its effect on adriamycin-resistant breast cancer cells.
  
  
  METHODS
  An adriamycin-resistant human breast cancer cell line, MCF-7/ADR cells were exposed to different concentrations of PS VII (0-100 μmol/L). Then, flow cytometric assays and a human apoptosis array were used to detect apoptotic cells and apoptosis related protein expression. P-glycoprotein levels and intracellular rhodamine 123 (RH-123) accumulations were measured to evaluate the expression and activity of P-glycoprotein.
  
  
  RESULTS
  PS VII dose dependently suppressed cell viability as well as triggered apoptosis and modulated drug resistance of MCF-7/ADR cells. Further results showed that PS VII treatment in MCF-7/ADR cells led to increased TNFR1, TRAIL R1/DR4, TRAIL R2/DR5, and FADD expression, and activation of PARP, caspase-8, and 3. In parallel to the alterations, P-glycoprotein expression and activity were also reduced.
  
  
  CONCLUSIONS
  These findings showed that PS VII might be an effective tumouristatic agent for the treatment of MDR breast cancer.
authors.affiliation: No. 422 Hospital of PLA, Zhanjiang 524005, Guangdong, PR China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Radiation Medicine, the Fourth Military Medical University, Xi׳an 710032, Shaanxi, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Miao
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, No. 309 Hospital of PLA, Beijing 100000, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Meng
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Pathogen Biology and Immunology, Xi'an Medical University, Xi'an, PR China.
authors.forename: Dian
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China. Electronic address: 1547223183@qq.com.
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Yue
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China. Electronic address: qbmei53@hotmail.com.
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D031446:Trillium / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; C000596536:Paris saponin VII; D012503:Saponins; D004317:Doxorubicin
keywords: Apoptosis; Growth inhibition; Multidrug resistance (MDR); P-glycoprotein (P-gp); Paris saponin VII