title: The plant extract of Pao pereira potentiates carboplatin effects against ovarian cancer.
abstract: BACKGROUND
  Herbal preparation of Pao pereira [Geissospermum vellosii Allem (Apocynaceae)] has long been used by oncologic patients and Integrative Medicine practitioners in South America. However, its anticancer activities have not been systematically studied.
  
  
  OBJECTIVE
  To investigate the anticancer effects of β-carboline alkaloids-enriched extract from Pao pereira (Pao), either alone or in combination with carboplatin, in preclinical ovarian cancer models.
  
  
  METHODS
  Cytotoxicity of Pao (0-800 µg/ml) against different ovarian cancer cell lines and an immortalized epithelial cell line was detected by flow cytometry, MTT assay and colony formation in soft agar. Combination of Pao and carboplatin, a primary chemotherapeutic drug for ovarian cancer, was evaluated using Chou-Talalay's methods. Mice bearing intraperitoneally spread ovarian cancer were treated with 20 or 50 mg/kg/day Pao by i.p. injection. Carboplatin at 15 mg/kg/week i.p. was compared and combined to Pao treatments.
  
  
  RESULTS
  Pao selectively inhibited ovarian cancer cell growth with IC₅₀ values of 180-235 µg/ml, compared to 537 µg/ml in normal cells. Pao induced apoptosis dose- and time-dependently and completely inhibited colony formation of tumor cells in soft agar at 400 µg/ml. Pao greatly enhanced carboplatin cytotoxicity, with dose reduction (DRIs) for carboplatin at 1.2-10 fold. In vivo, Pao alone suppressed tumor growth by 79% and decreased volume of ascites by 55%. When Pao was combined with carboplatin, tumor inhibition reached 97% and ascites was completely eradicated.
  
  
  CONCLUSIONS
  Pao possess potent antitumor activity and could enhance carboplatin effect, and therefore holds therapeutic potential in the treatment of ovarian cancer.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, KU Integrative Medicine, University of Kansas Medical Center , Kansas City, KS , USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D029062:Apocynaceae / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007274:Injections, Intraperitoneal; D008519:Medicine, Traditional; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D013020:South America; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D016190:Carboplatin