Fig. 6

Illustrative diagram related to mechanisms of gossypol-induced decrease in cancer cell viability. The figure illustrates the multifaceted mechanisms by which gossypol reduces the viability of cancer cells. Gossypol inhibits TNF-α, which in turn prevents the activation of NF-kB, a transcription factor that regulates genes responsible for cell survival and proliferation. Additionally, gossypol disrupts the Nrf2/ARE pathway within the nucleus, leading to decreased DNA transcription of survival genes. It also inhibits the ICAM-1 pathway, contributing to reduced inflammation and interference with cancer cell adhesion. Gossypol's interaction with CUL4 appears to promote the degradation of survival proteins, further inducing cell death. Moreover, it suppresses NOXA, a pro-apoptotic protein, and induces the generation of ROS, leading to oxidative stress and damage. Collectively, these actions lead to a decrease in cancer cell viability. ARE Antioxidant Response Element, CUL4 Cullin 4, ICAM-1 Intercellular Adhesion Molecule 1, IL-6 Interleukin 6, NF-kB Nuclear Factor kappa-light-chain-enhancer of activated B cells, NOXA Phorbol-12-myristate-13-acetate-induced protein 1, Nrf2 Nuclear Factor Erythroid 2–Related Factor 2, ROS Reactive Oxygen Species, TLR4 Toll-Like Receptor 4, TNF-α Tumor Necrosis Factor alpha. Symbols: ↓decrease, X inhibition