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Indexed by:Journal Papers

Date of Publication:2019-09-01

Journal:PHARMACOLOGICAL RESEARCH

Included Journals:PubMed、SCIE

Volume:147

Page Number:104387

ISSN No.:1043-6618

Key Words:Daidzein; Topotecan; Breast cancer; ER alpha; Drug resistance; Topoisomerase I

Abstract:Topotecan (TPT), a semisynthetic derivative of camptothecin, has been used in cancer chemotherapy, but side effects and drug resistance limit its clinical application. Daidzein (DAI), a natural isoflavone and bioactive food component widely existing in fruits, nuts, soybeans and soy-based products, is a type of phytoestrogen. Combination treatment with DAI and TPT showed a strong synergistic effect on tumor cells, with a 0.10(similar to)0.66 combined index, by increasing TPT inhibition on Topo I, resulting in more cells arresting at the G2/M phase and inducing more cells to undergo apoptosis. In addition, the resistance of MCF7/ADR cells to TPT was reversed (the resistance index decreased from 7.17 to 0.77) by inhibiting the expression of ER alpha and BCRP to increase TPT accumulation intracellularly. Moreover, the combination of DAI and TPT showed a stronger inhibitory effect (P < 0.01) on tumor growth in both MCF7 and MCF7/ADR xenograft models than the 9 mg/kg TPT monotherapy group. Our results may provide a reasonable, new approach to develop safe and efficient nutrition components from foods for breast cancer combination treatment.