Quercetin and tumor microenvironment associated pathways in lung cancer: a network pharmacology and in vitro study
- 1epartment of Pharmacology, C.L. Baid Metha College of Pharmacy, Chennai, India
Abstract
Cancer progression is initiated by genetic mutations but is largely sustained by tumor microenvironment (TME)-mediated epigenetic regulation, which promotes cancer cell survival, adaptation, immune evasion, metabolic adaptation, and therapeutic resistance. This study investigated the potential of Quercetin as a tumor microenvironment-oriented therapeutic agent in non-small cell lung cancer (NSCLC) using network pharmacology, molecular docking, and clonogenic assay. Network pharmacology identified 98 overlapping targets between Quercetin and NSCLC. Pathway enrichment analysis identified key therapeutic targets, particularly hypoxia-inducible factor (HIF)- and cortisol-related pathways involved in TME regulation. Molecular docking demonstrated favorable binding of Quercetin with HIF and cortisol-related targets (CRHR1, NR3C1, EP300, and VHL), supporting its interactions with cortisol signaling, and hypoxia-related pathways. Furthermore, the potential of Quercetin to suppress clonogenic survival associated with cancer relapse was evaluated using the A549 cell line. Simultaneous treatment with 11.73 μg/mL Doxorubicin and 22.98 μg/mL Quercetin reduced colony formation from 39 to 8.5 colonies per field, indicating reduced clonogenic survival and enhanced chemosensitivity. These findings suggest an alternative approach in which Quercetin may complement conventional chemotherapy by targeting tumor microenvironment-associated pathways, with the potential to suppress long-term cancer cell survival and colony formation that usually occur post-chemotherapy.
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BibTeX
@article{yazhini2026quercetin,
title = {{Quercetin and tumor microenvironment associated pathways in lung cancer: a network pharmacology and in vitro study}},
author = {Yazhini and Senthil Kumar and Sabbathyan Balla and Thasna and Shyam and Praveen Kumar and Joses Robertson},
journal = {Oncology Reviews},
year = {2026},
month = nov,
doi = {10.3389/or.2026.1680291},
url = {https://doi.org/10.3389/or.2026.1680291},
note = {CC BY},
}
RIS
TY - JOUR
TI - Quercetin and tumor microenvironment associated pathways in lung cancer: a network pharmacology and in vitro study
AU - Yazhini
AU - Senthil Kumar
AU - Sabbathyan Balla
AU - Thasna
AU - Shyam
AU - Praveen Kumar
AU - Joses Robertson
PY - 2026
DA - 2026/11/03
JO - Oncology Reviews
DO - 10.3389/or.2026.1680291
UR - https://doi.org/10.3389/or.2026.1680291
AB - Cancer progression is initiated by genetic mutations but is largely sustained by tumor microenvironment (TME)-mediated epigenetic regulation, which promotes cancer cell survival, adaptation, immune evasion, metabolic adaptation, and therapeutic resistance. This study investigated the potential of Quercetin as a tumor microenvironment-oriented therapeutic agent in non-small cell lung cancer (NSCLC) using network pharmacology, molecular docking, and clonogenic assay. Network pharmacology identified 98 overlapping targets between Quercetin and NSCLC. Pathway enrichment analysis identified key therapeutic targets, particularly hypoxia-inducible factor (HIF)- and cortisol-related pathways involved in TME regulation. Molecular docking demonstrated favorable binding of Quercetin with HIF and cortisol-related targets (CRHR1, NR3C1, EP300, and VHL), supporting its interactions with cortisol signaling, and hypoxia-related pathways. Furthermore, the potential of Quercetin to suppress clonogenic survival associated with cancer relapse was evaluated using the A549 cell line. Simultaneous treatment with 11.73 μg/mL Doxorubicin and 22.98 μg/mL Quercetin reduced colony formation from 39 to 8.5 colonies per field, indicating reduced clonogenic survival and enhanced chemosensitivity. These findings suggest an alternative approach in which Quercetin may complement conventional chemotherapy by targeting tumor microenvironment-associated pathways, with the potential to suppress long-term cancer cell survival and colony formation that usually occur post-chemotherapy.
SN - 1970-5557
SN - 1970-5565
ER -