The plant extract of Pao pereira potentiates carboplatin effects against ovarian cancer

Abstract

Context: 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.Materials and 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.Discussion and conclusion: Pao possess potent antitumor activity and could enhance carboplatin effect, and therefore holds therapeutic potential in the treatment of ovarian cancer.