Modulation of cytochrome P450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism

Modulation of cytochrome P450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism

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...

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Main Author: Fen, Yong Ya
Format: Thesis
Language:English
Published: 2020
Subjects:
R Medicine
Online Access:http://eprints.usm.my/48083/1/55.%20YONG%20YA%20FEN-FINAL%20THESIS%20P-UM001017%28R%29%20PWD_-24%20pages.pdf
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spelling my-usm-ep.480832021-01-12T08:47:32Z Modulation of cytochrome P450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism 2020-07 Fen, Yong Ya R Medicine 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. 2020-07 Thesis http://eprints.usm.my/48083/ http://eprints.usm.my/48083/1/55.%20YONG%20YA%20FEN-FINAL%20THESIS%20P-UM001017%28R%29%20PWD_-24%20pages.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Perubatan
institution Universiti Sains Malaysia
collection USM Institutional Repository
language English
topic R Medicine
spellingShingle R Medicine
Fen, Yong Ya
Modulation of cytochrome P450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism
description 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.
format Thesis
qualification_level Master's degree
author Fen, Yong Ya
author_facet Fen, Yong Ya
author_sort Fen, Yong Ya
title Modulation of cytochrome P450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism
title_short Modulation of cytochrome P450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism
title_full Modulation of cytochrome P450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism
title_fullStr Modulation of cytochrome P450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism
title_full_unstemmed Modulation of cytochrome P450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism
title_sort modulation of cytochrome p450s by strobilanthes crispus anticancer sub-fraction and its potential interaction with tamoxifen metabolism
granting_institution Universiti Sains Malaysia
granting_department Pusat Pengajian Sains Perubatan
publishDate 2020
url http://eprints.usm.my/48083/1/55.%20YONG%20YA%20FEN-FINAL%20THESIS%20P-UM001017%28R%29%20PWD_-24%20pages.pdf
_version_ 1747821878338125824

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