Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin

Abstract

Quercetin is an antioxidant phytochemical which belongs to the natural flavonoids group. Recently, the compound has been reported to inhibit glutathione reductase responsible for replenishing reduced forms of glutathione and thus leads to glutathione depletion, triggering cell death. In this study, we examined if quercetin sensitizes tumors to oxaliplatin by inhibiting glutathione reductase activity in human colorectal cancer cells, and thereby facilitates apoptotic cell death. A combined treatment with quercetin and oxaliplatin was found to synergistically inhibit glutathione reductase activity, lower intracellular glutathione level, increase reactive oxygen species production, and reduce cell viability, compared to treatment with oxaliplatin alone in human colorectal HCT116 cancer cells. Furthermore, the incorporation of sulforaphane, recognized for its ability to scavenge glutathione, in combination with quercetin and oxaliplatin, substantially suppressed tumor growth in an HCT116 xenograft mouse model. These findings suggest that the depletion of intracellular glutathione by quercetin and sulforaphane could strengthen the anti-cancer efficacy of oxaliplatin.

The Preparation, Functional Properties, and Application of Food-Derived Antioxidants and Anti-Inflammatory Agents

“…This aligns perfectly with the intriguing study on quercetin [ 7 ] included in this Special Issue, which suggests it may enhance the effectiveness of cancer treatments by influencing cellular pathways. These findings underscore the intricate link between dietary choices, gut health, and overall disease resistance.…”

Role of natural products in tumor therapy from basic research and clinical perspectives

“…Quercetin and its fermented extract exhibited excellent inhibitory effect on the viability of BPA-exposed HT29 colon cancer cells [33]. Additionally, quercetin enhanced the chemotherapeutic impact of oxaliplatin in HCT116 cells by increasing intracellular ROS through its suppressive action on glutathione levels [34]. Moreover, amalgamation of quercetin with anastrozole and capecitabine induce activation of caspase 3 expression in vitro [35].…”

The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment

“…Additionally, fermented quercetin also augments the cytotoxicity and efficacy of the anticancer drug 5-fluorouracil [ 110 ]. Compared to using oxaliplatin alone to treat human CRC cells (HT29), combined treatment with quercetin and oxaliplatin synergistically inhibits glutathione reductase activity, reduces intracellular glutathione levels, increases reactive oxygen species production, and decreases cell viability, thereby enhancing the anticancer efficacy of oxaliplatin [ 160 ]. Pre-treatment with quercetin significantly enhances cisplatin-induced apoptosis in HT-29 cells, thereby improving the anticancer function of cisplatin during CRC chemotherapy.…”