TY - JOUR
T1 - Reduction of breast tumor drug resistance by 2,3,5,4'-tetrahydroxystilbene for exhibition synergic chemotherapeutic effect
AU - Chang, Yao Yuan
AU - Lin, Hung Jun
AU - Hsiao, Ling Chi
AU - Lin, Yu Feng
AU - Chang, Chih Sheng
AU - Liu, Der Zen
N1 - Funding Information:
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.
Publisher Copyright:
© 2021 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/12
Y1 - 2021/12
N2 - 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-Obeta- 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.
AB - 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-Obeta- 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.
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U2 - 10.1371/journal.pone.0260533
DO - 10.1371/journal.pone.0260533
M3 - Article
AN - SCOPUS:85121245722
SN - 1932-6203
VL - 16
JO - PLoS ONE
JF - PLoS ONE
IS - 12 December
M1 - e0260533
ER -
