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

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.

2,3,5,4′-Tetrahydroxystilbene (TG1), a Novel Compound Derived from 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG), Inhibits Colorectal Cancer Progression by Inducing Ferroptosis, Apoptosis, and Autophagy

“…Natural products are important sources of innovative drug development [38], but clinical applications are limited due to poor bioavailability or severe toxicity [39]. TG1, modified from 2,3,5,4tetrahydroxystilbene-2-O-β-D-glucoside (THSG) via deglucosylation, has been proven to have low toxicity in vitro and in vivo, while this modification may improve the drug potency via the reduction of the drug efflux effect [30]. Further, our results found that the cytotoxic effect of TG1 on CRC cells does not only come from inducing apoptosis, but more importantly, it regulates the induction of ferroptosis.…”

“…A new small molecule drug called TG1 has been developed for versatile drug applications. It has been shown to have low toxicity and promote cytotoxicity in breast cancer cells when used in combination with chemotherapeutic drugs [30]. However, until now, the role of TG1 in inducing cytotoxic effects on CRC and the underlying mechanisms and downstream signaling have been unknown.…”