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.

• Anticancer
• combination therapy
• natural product
• synergy

Acknowledgements

This study was supported by a grant from the Beljanski Foundation and the plant extract was provided by Natural Source International Ltd. The authors have no affiliation or financial relationship with the sponsor. Neither the Beljanski Foudation nor Natural Source International Ltd. played a role in the design and conduction of the study and preparation of the manuscript.