Please use this identifier to cite or link to this item: https://ptsldigital.ukm.my/jspui/handle/123456789/485634
Title: Evaluation of estrogenic activity and mechanistics action of marantodes pumilum (blume), mimosa pudica L. and persicaria hydropiper L. delarbre in MCF-7 breast cancer cell line
Authors: A.K.M. Moyeenul Huq (P63476)
Supervisor: Jamia Azdina Binti Jamal, Associate Prof. Dr.
Keywords: Hormone replacement therapy
Breast cancer
Endometrial cancer
Dissertations, Academic -- Malaysia
Issue Date: 18-Sep-2017
Description: Hormone replacement therapy for postmenopausal symptoms has been associated with potential risks of breast and endometrial cancer. P. hydropiper, M. pudica, and M. pumilum have traditional uses for women's reproductive problems. However, there has been lack of studies to scientifically prove whether they have potentiality to alleviate symptoms of postmenopausal disorders and how they work. Hence, the aim of this study was to evaluate their estrogenicity and mechanistic action using several re-established and optimised assays. Sequentially extracted crude fractions of hexane, dichloromethane, methanol and aqueous were prepared from M. pudica and P. hydropiper whole plant. While, 50%ethanol and aqueous extracts of leaves and stem-roots of three varieties of M. pumilum were prepared. The phytochemicals, dimethylbelamcandaquinone B (DPA1) and 1,3-dihydroxy-5-[10(Z)-pentadecenyl] benzene (DPA2) were isolated from M. pumilum var. alata and mimosine from M. pudica. Twenty extracts and three compounds were tested for estrogenicity by MCF-7 cell proliferation. The binding of bioactive extracts and compounds to ERα receptor was measured through the recruitment of SRC1 co-activator to the ERα-ligand complex. Consecutively, the ER transactivation activity of ERE and the expression of TFF1 and PGR marker genes were also evaluated. Finally, docking was performed for the bioactive compounds with the ERα. Results demonstrated that a significant estrogen dependent proliferation of MCF-7 cells for M. pudica dichloromethane and M. pumilum var. alata leaf aqueous extracts (p<0.01, respectively) as well as for mimosine (p<0.05). DPA1 (p<0.001), DPA2 (p<0.05). Following that, M. pudica dichloromethane fraction and mimosine showed ER dependent proliferation when co-treated with tamoxifen (p<0.001). Later, the dichloromethane fraction of M. pudica and mimosine showed increased recruitment of SRC1 (p<0.05) to ERα-ligand complex. Only M. pudica dichloromethane fraction showed ERE transactivation activity (p<0.01). TFF1 and PGR genes were significantly expressed by both the extracts (p<0.01) and the compounds, DPA1 (p<0.05), DPA2 (p<0.05) and mimosine (p<0.001), suggesting ER mediated activity. Docking showed moderate interactions of only DPA2 and mimosine at the ERα binding site. In conclusion, M. pudica, M. pumilum var. alata, DPA1, DPA2 and mimosine mimic estrogenic activity through ER-dependent genomic pathway and potentially be developed further to help alleviate the symptoms of postmenopausal disorders.,Ijazah Doktor Falsafah
Pages: 124
Call Number: QV20.5.H958e 2017 9
Publisher: UKM, Kuala Lumpur
Appears in Collections:Faculty of Pharmacy / Fakulti Farmasi

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