Date of Defense
9-4-2026 1:30 PM
Location
Microsoft Teams
Document Type
Thesis Defense
Degree Name
Master of Science in Molecular Biology and Biotechnology
College
COS
Department
Biology
First Advisor
Prof. Synan F. AbuQamar
Keywords
Chemotherapy, flavonoids, Epigallocatechin-3-O-gallate (EGCG), Quercetin, Human fibroblast cells (F-180), Reactive oxygen species (ROS), Nrf2 antioxidant pathway.
Abstract
Chemotherapy remains the primary treatment strategy for cancers; however, its clinical efficacy is often limited by severe toxic effects resulting in normal cells. The study investigated the protective potential of the flavonoids epigallocatechin-3-O-gallate (EGCG) and quercetin, used in combination, against chemotherapy-induced toxicity in human fibroblast F-180 cells. Cells were exposed to three commonly used chemotherapeutic agents, doxorubicin, cisplatin, and etoposide, in the presence or absence of EGCG and quercetin at concentrations of 25 and 50 μM. cells viability was assessed using the MTT assay, while oxidative stress and antioxidant capacity were evaluated by intracellular reactive oxygen species (ROS) and total antioxidant capacity (T-AOC) assays. Molecular mechanisms were further explored through quantitative real-time PCR and Western blotting to examine modulation of Nrf2 antioxidant signaling pathway. The results demonstrated that treatment with chemotherapeutic drugs alone significantly reduced F-180 cell viability and increased intracellular ROS levels. Cotreatment with EGCG and quercetin significantly improved fibroblast cell viability, compared to drugonly treatments, while not protecting MCF-7 breast cancer cells from chemotherapy-induced cytotoxicity. ROS levels were markedly reduced following flavonoid co-treatment and were accompanied by a significant enhancement in total antioxidant capacity. At the molecular level, EGCG and quercetin co-treatment upregulated Nrf2 mRNA expressions in addition to the expression of downstream antioxidant genes, including SOD1, GPX1, catalase, and P53. These findings indicate activation of the Nrf2-mediated cytoprotective response and attenuation of oxidative stress-induced cellular damage. Overall, this study demonstrates that combined EGCG and quercetin treatment confers selective protection to normal human fibroblast cells against chemotherapy-induced toxicity without compromising the cytotoxic efficacy of chemotherapeutic agents against cancer cells. These findings support the potential use of dietary flavonoids as adjuvant agents to reduce chemotherapyassociated side effects and improve patient quality of life.
Included in
STUDYING THE ROLE OF COMBITIONAL FLAVONOIDS AGAINST TOXICITY OF CHEMOTHRAPEUTIC DRUGS IN HUMAN FIBROBLAST CELLS
Microsoft Teams
Chemotherapy remains the primary treatment strategy for cancers; however, its clinical efficacy is often limited by severe toxic effects resulting in normal cells. The study investigated the protective potential of the flavonoids epigallocatechin-3-O-gallate (EGCG) and quercetin, used in combination, against chemotherapy-induced toxicity in human fibroblast F-180 cells. Cells were exposed to three commonly used chemotherapeutic agents, doxorubicin, cisplatin, and etoposide, in the presence or absence of EGCG and quercetin at concentrations of 25 and 50 μM. cells viability was assessed using the MTT assay, while oxidative stress and antioxidant capacity were evaluated by intracellular reactive oxygen species (ROS) and total antioxidant capacity (T-AOC) assays. Molecular mechanisms were further explored through quantitative real-time PCR and Western blotting to examine modulation of Nrf2 antioxidant signaling pathway. The results demonstrated that treatment with chemotherapeutic drugs alone significantly reduced F-180 cell viability and increased intracellular ROS levels. Cotreatment with EGCG and quercetin significantly improved fibroblast cell viability, compared to drugonly treatments, while not protecting MCF-7 breast cancer cells from chemotherapy-induced cytotoxicity. ROS levels were markedly reduced following flavonoid co-treatment and were accompanied by a significant enhancement in total antioxidant capacity. At the molecular level, EGCG and quercetin co-treatment upregulated Nrf2 mRNA expressions in addition to the expression of downstream antioxidant genes, including SOD1, GPX1, catalase, and P53. These findings indicate activation of the Nrf2-mediated cytoprotective response and attenuation of oxidative stress-induced cellular damage. Overall, this study demonstrates that combined EGCG and quercetin treatment confers selective protection to normal human fibroblast cells against chemotherapy-induced toxicity without compromising the cytotoxic efficacy of chemotherapeutic agents against cancer cells. These findings support the potential use of dietary flavonoids as adjuvant agents to reduce chemotherapyassociated side effects and improve patient quality of life.