10-Gingerol Enhances the Effect of Taxol in Triple-Negative Breast Cancer via Targeting ADRB2 Signaling

Abstract

Although paclitaxel is widely used in cancer treatment, severe side effects and drug resistance limit its clinical use. 10gingerol (10-G) is a natural compound isolated from ginger, which displays anti-inflammatory, antioxidant, and antiproliferative properties. However, the chemotherapy-sensitization effect of 10-G on triple-negative breast cancer (TNBC) has not been fully clarified. This study is aimed at investigating the effect of 10-G on the paclitaxel sensitivity in TNBC, and its underlying mechanism. Methods: The study was determined through in vitro and in vivo experiments. Cell viability and proliferation were detected by cell counting kit 8 (CCK-8) and colony formation. To detect cell apoptosis, flow cytometry and TUNEL were used. The expression of proteins was detected by Western blotting and immunohistochemistry. The molecular docking and gene knockout were corroborated by interactions between 10-G and adrenoceptor Beta 2 (ADRB2). The body weight of mice, histopathology and organs (kidney and spleen) coefficients were used to monitor the drug toxicities. Results: In vitro, 10-G increased the sensitivity of TNBC cells to paclitaxel, and could synergistically promote the apoptosis of TNBC cells induced by paclitaxel. In combination with molecular docking and lentivirus knockdown studies, ADRB2 was identified as a 10-G binding protein. 10-G inhibited ADRB2 by binding to the active site of ADRB2. Knockdown of ADRB2 reduces the proliferation activity of TNBC cells but also attenuates the sensitizing effects of 10-G to paclitaxel. Western blotting and immunohistochemistry showed that 10-G played an anti-proliferation and chemotherapy-sensitizing role by inhibiting the ADRB2/ERK signal. Toxicity evaluation showed that 10-G would not increase hepatorenal toxicity with paclitaxel. Conclusion: This data suggests that 10-G may be used as a new chemotherapeutic synergist in combination with paclitaxel to enhance anticancer activity. The potential value of ADRB2 as a target for improving chemotherapy sensitivity was also emphasized.

Exploring the mechanism of an active ingredient of ginger, dihydrocapsaicin, on triple negative breast cancer based on network pharmacology and in vitro experiments

“…The medicinal part is the fresh rhizome of Zingiberaceae plant ginger ( 7 ), which have the effects of relieving cold, warming and stopping vomiting, resolving phlegm and relieving cough. It contains gingerol, gingerol, polyphenol, turmeric ketone and other bioactive components, which have been reported to have anti-inflammatory and anti-tumor effects ( 8 – 11 ), paclitaxel synergist has also been studied to improve the clinical treatment of TNBC ( 12 ). Ginger's pharmacological effects and edible characteristics highlight its different effects on cancer and normal cells, which has broad prospects in clinical application.…”

Pharmacological Studies of Medicinal Potential Phytochemicals in Plant Roots

“…Currently, the main trend in this branch of science is to discover new formulations, innovative molecular structures and derivatives of known substances found in various parts of plants, and to find their new applications [3][4][5][6]. In vitro and in vivo pre-clinical trials have shown that herbal drugs can interact with other drugs, such as chemotherapeutics used for cancer treatment, increasing their therapeutic efficacy [7,8]. Nevertheless, both single compounds and multicomponent formulations, except for their therapeutic effects, may also have adverse effects.…”