Combined Therapeutic Potential of Thymoquinone and Theaflavin Through P13k Pathway Suppression

Abstract

Background: The synergistic potential of natural phytochemicals in modulating key cancer related pathways offers a promising approach for therapeutic development. This study investigates the combined anti-cancer, anti-inflammatory, and antioxidant effects of Thymoquinone and theaflavin on KB cells. 

Methods: Thymoquinone and theaflavin were evaluated individually and in combination (1:1,2:1,1:2) across a concentration range of 1 to 200 µg/mL. Cytotoxicity was assessed by MTT assay, anti-inflammatory activity was measured using Bovine serum albumin method, and antioxidant potential was determined via the DPPH radical scavenging assay. Gene expression analysis of P13K, Akt, mTOR, NF-kB, IL-6, Bcl-2 and BAX was performed using real-time PCR. 

Results: Combination treatments, especially at a 1:1 ratio, demonstrated significantly enhanced cytotoxicity, superior inhibition of protein denaturation, and greater DPPH radical scavenging compared to individual compounds. Gene expression analysis revealed strong downregulation of the P13K/Akt/mTOR and NF-kB/IL-6 pathways and a shift toward apoptosis characterised by decreased Bcl-2 and increased BAX expression. 

Conclusion: The synergistic interaction between Thymoquinone and theaflavin effectively modulates survival, inflammatory, and apoptotic pathways, offering a promising natural combination strategy for anticancer and anti-inflammatory therapies. Further preclinical investigations are warranted to validate their clinical applicability.