Fen, Yong Ya
(2020)
Modulation of cytochrome P450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism.
Masters thesis, Universiti Sains Malaysia.
Abstract
The anticancer property of Strobilanthes crispus (S. crispus) suggests its
potential benefit as an adjuvant in breast cancer treatment. Potential herb-drug
interaction (HDI) has always been a safety concern in pharmacotherapy as alteration
in cytochrome P450 (CYP) mediated metabolism may lead to treatment failure and
toxicity. In this study, the in vitro modulatory effect of a standardized sub-fraction of
S. crispus (F3) on five human CYPs (CYP2B6, CYP2C9, CYP2C19, CYP2D6 and
CYP3A4) was first investigated. Negligible inhibitory effects of F3 on all the five
CYPs were observed, with IC50 values more than 100-fold higher in comparison to
known CYP inhibitors. The use of F3 in conjunction with conventional breast cancer
therapy using tamoxifen (TAM) could be a strategy to maximize the therapeutic
efficacy. Thus, the investigation of the interaction between F3 and TAM is crucial.
The potential HDI was first investigated through evaluating the influence of F3 on
CYP mediated TAM metabolism in vitro. F3 demonstrated weak mixed-type
inhibition towards CYP2D6 catalyzed TAM 4-hydroxylation and CYP3A4 catalyzed
TAM N-desmethylation. The combined effect of TAM and F3 on the viability of MCF-
7 cell line was then investigated. A buffering antagonistic effect was observed from
the combined treatment. The outcome of this study suggests the low possible
interactions between F3 and TAM as well as the five CYPs catalyzed drug metabolism.
Nevertheless, further studies are warranted to evaluate the efficiency and safety of the
drug combination treatment in vivo.
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