Reduction of breast tumor drug resistance by 2,3,5,4'-tetrahydroxystilbene for exhibition synergic chemotherapeutic effect

Yao-Yuan Chang; Hung-Jun Lin; Ling-Chi Hsiao; Yu-Feng Lin; Chih-Sheng Chang; Der-Zen Liu

doi:10.1371/journal.pone.0260533

Reduction of breast tumor drug resistance by 2,3,5,4'-tetrahydroxystilbene for exhibition synergic chemotherapeutic effect

PLoS One. 2021 Dec 7;16(12):e0260533. doi: 10.1371/journal.pone.0260533. eCollection 2021.

Authors

Yao-Yuan Chang¹, Hung-Jun Lin¹, Ling-Chi Hsiao¹, Yu-Feng Lin², Chih-Sheng Chang³, Der-Zen Liu^{1

4}

Affiliations

¹ Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
² Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
³ Department of Horticulture Science, National Chiayi University, Chiayi City, Taiwan.
⁴ Medical and Pharmaceutical Industry Technology and Development Center, New Taipei, Taiwan.

Abstract

Chemotherapy drugs have limited efficacy in breast cancer due to multidrug resistance generated by cancer cells against anticancer drugs. In this study, we developed a novel derivative, 2, 3, 5, 4'-tetrahydroxystilbene (TG1) by modifying 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG). In-vivo zebrafish embryo tests revealed that TG1 showed low toxicity. The equitoxic combination of DOX or DTX with TG1 in MCF-7/Adr reduced the IC50 of DOX or DTX, and the combination index (CI) showed strong synergistic effects in the 1:3 molar ratio of DTX: TG1 and 1:5 molar ratio of DOX: TG1. Moreover, fluorescence images confirmed the cellular uptake of DOX when combined with TG1 in MCF-7/Adr. Western blotting analysis indicated downregulation of p-glycoprotein (P-gp) after MCF-7/Adr treated with TG1. In conclusion, the combined therapy of DTX or DOX and TG1 increases drug efficacy via suppressing the p-glycoprotein efflux pump. These results suggest that TG1 may have potential use for breast cancer patients, especially those with multidrug resistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / metabolism
Animals
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Docetaxel / pharmacology*
Doxorubicin / pharmacology*
Drug Resistance, Neoplasm / drug effects*
Drug Synergism
Female
Gene Expression Regulation, Neoplastic / drug effects
Glucosides / pharmacology*
Humans
MCF-7 Cells
Stilbenes / pharmacology*
Zebrafish

Substances

ABCB1 protein, human
ATP Binding Cassette Transporter, Subfamily B
Glucosides
Stilbenes
2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside
Docetaxel
Doxorubicin

Grants and funding

The list of funders were - Ministry of Science and Technology, Taiwan, MOST105-2221-E-038-003-MY3 for Der-Zen Liu - Ministry of Science and Technology, Taiwan, MOST107-2314-B-038-033-MY3 for Der-Zen Liu - Agricultural Technology Research Institute (TW), 10710025 for Hung-Jun Lin And the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.