統合腫瘍学ジャーナル

Assessment of Dong Quai Hepatic Metabolism and Potential Interactions when Combined with Chemotherapy

Abstract

Xue Zhang, Anjali Gaikwad, Lata Mathew, Larry Coffer, John Dalrymple and Judith A Smith

Background: Dong Quai is a common herbal supplement classified as a “phytoestrogen” used for the improvement of female reproductive function. In the oncology setting, women often seek natural approaches for managing symptoms associated with decreased hormone levels either from surgery or chemotherapy-induced. Clinically, the concern is the safety of phytoestrogens in combination with chemotherapy. The objective of this study was to characterize the hepatic metabolism of Dong Quai to define the potential for drug interactions with selected chemotherapy agents and its impact on alterations in the cytotoxicity in panel of human cancer cell lines.
Methods: In vitro high through-put cytochrome P450 (CYP450) inhibition assay was performed for CYP450 2C9, 2C8, 2D6 and 3A4 isoenzymesto evaluate phase I metabolism of Dong Quai alcohol-free extract. An ex vivo hepatic induction assay with human hepatocytes was used to determine whether Dong Quai is an inducer of CYP450 isoenzymes. The potential cytotoxic effects of Dong Quai alone and its effect when combined with selected chemotherapies were evaluated by a growth inhibition assay in a panel of eight human cancer cell lines.
Results: No inhibition of CYP450 was observed in presence of Dong Quai. At an estimated clinical relevant concentration of 0.86 mg/mL, Dong Quai demonstrated Quai induced CYP3A4, 2C9, 2C8 and 2D6. Dong Quaidid not demonstrated cytotoxicity by itself in the panels of eight human cancer cell lines with 50% growth inhibition was not achieved. The 25% growth inhibition was achieved at concentrations ranging from 0.39 mg/mL to 4.48 mg/mL. Combination growth inhibition assays showed decreased cytotoxic activity of chemotherapy agents.
Conclusion: This data suggests that Dong Quai is an inducer of the CYP450 pathways and also decreased cytotoxic activity of selected chemotherapy. Until confirmatory in vivo information available Dong Quai should be used with caution with chemotherapy.