title: Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells.
abstract: Intraperitoneal chemotherapy together with cytoreductive surgery is the standard of care for a number of peritoneal surface malignancies. However, this approach fails to maintain the complete response and disease recurs due to microscopic residual disease. Although safer than systemic chemotherapy regimens, locoregional treatment with chemotherapeutics can induce toxicity which is a major concern affecting the patient's treatment protocol and outcome. For an enhanced treatment efficacy, efforts should be made to maximize cytotoxic effects of chemotherapeutic agents on tumor cells while minimizing their toxic effects on host cells. Bromelain and N-acetylcysteine are two natural agents with good safety profiles shown to have anti-cancer effects. However, their interaction with chemotherapeutics is unknown. In this study, we investigated if these agents have the potential to sensitize in vitro gastrointestinal cancer models to cisplatin, paclitaxel, 5-fluorouracil, and vincristine. The drug-drug interaction was also analyzed. Our findings suggest that combination of bromelain and N-acetylcysteine with chemotherapeutic agents could give rise to an improved chemotherapeutic index in therapeutic approaches to peritoneal surface malignancies of gastrointestinal origin so that maximum benefits could result from less toxic and more patient-friendly doses. This represents a potentially efficacious strategy for the enhancement of microscopic cytoreduction and is a promising area for future research.
authors.affiliation: Department of Surgery, St George Hospital, The University of New South Wales Gray Street, Kogarah, Sydney NSW 2217, Australia.
authors.forename: Afshin
authors.initials: A
authors.lastname: Amini
authors.affiliation: Department of Surgery, St George Hospital, The University of New South Wales Gray Street, Kogarah, Sydney NSW 2217, Australia.
authors.forename: Samar
authors.initials: S
authors.lastname: Masoumi-Moghaddam
authors.affiliation: Department of Surgery, St George Hospital, The University of New South Wales Gray Street, Kogarah, Sydney NSW 2217, Australia.
authors.forename: Anahid
authors.initials: A
authors.lastname: Ehteda
authors.affiliation: Cancer Care Center, St George Hospital, The University of New South Wales Gray Street, Kogarah, Sydney NSW 2217, Australia.
authors.forename: Winston
authors.initials: W
authors.lastname: Liauw
authors.affiliation: Department of Surgery, St George Hospital, The University of New South Wales Gray Street, Kogarah, Sydney NSW 2217, Australia.
authors.forename: David Lawson
authors.initials: DL
authors.lastname: Morris
keywords: 5-fluorouracil; N-acetylcysteine; bromelain; cisplatin; gastrointestinal cancers; paclitaxel; potentiation; vincristine