Quercetin: A Promising Flavonoid Enhancing Chemotherapy and Immunotherapy Synergy

Quercetin: A Promising Flavonoid Enhancing Chemotherapy and Immunotherapy Synergy

Quercetin is a plant-based flavonoid found in onions, apples, berries and tea that is garnering increasing attention for its potential role in cancer therapy. Recent clinical and pre-clinical studies highlight not only its direct anti-tumour effects, but also its ability to enhance the efficacy of chemotherapy and immunotherapy when used in combination.

Mechanistically, quercetin exerts multiple actions: it induces apoptosis (programmed cell death) in tumour cells, inhibits proliferation, and blocks metastatic processes. Key signalling pathways affected include PI3K/AKT, MAPK/ERK, JAK/STAT, Wnt/β-catenin and NF-κB. Quercetin also modifies gene expression via microRNAs and long non-coding RNAs, thereby influencing resistance pathways and tumour micro-environment.

In combination settings, quercetin has shown synergy with standard anti-cancer agents. For example, when combined with docetaxel in breast cancer cell lines it enhanced apoptosis, raised p53 and Bax levels, and reduced Bcl-2, p-AKT and STAT3 activity. These findings suggest that quercetin may improve treatment outcomes by both sensitizing tumour cells to chemotherapy and dampening tumour survival pathways.

While the data are promising, bioavailability is a significant challenge—quercetin is poorly absorbed in its natural form, so researchers are exploring delivery systems to enhance plasma levels and tumour penetration. Although not yet standard in oncology care, quercetin appears to be a compelling adjunctive candidate, particularly in integrative settings where boosting immune response and enhancing chemotherapy efficacy are priorities.

Reference:

Asgharian, P., Tazekand, A.P., Hosseini, K. et al. Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets. Cancer Cell Int 22, 257 (2022). https://doi.org/10.1186/s12935-022-02677-w

Safi A, Heidarian E, Ahmadi R. Quercetin Synergistically Enhances the Anticancer Efficacy of Docetaxel through Induction of Apoptosis and Modulation of PI3K/AKT, MAPK/ERK, and JAK/STAT3 Signaling Pathways in MDA-MB-231 Breast Cancer Cell Line. Int J Mol Cell Med. 2021 Winter;10(1):11-22. doi: 10.22088/IJMCM.BUMS.10.1.11. Epub 2021 May 22. PMID: 34268250; PMCID: PMC8256834.