Table 1 Overview of gossypol’s antitumor mechanisms

Apoptosis induction

Inhibits anti-apoptotic proteins (Bcl-2 family);

↑caspase-dependent/independent pathways

Induces apoptosis in various cancer cell types

[85]

Oxidative stress and mitochondrial dysfunction

↑ ROS, leading to DNA damage and mitochondrial dysfunction

Leads to cell apoptosis through oxidative stress

[80]

Epigenetic modulation and DNA damage

↑ DNA replication/mismatch proteins; ↓ polymerases α/β

Triggers apoptosis due to DNA damage

[25, 57]

Telomerase activity modulation

Modulates telomerase activity; Affects TERT through transcriptional downregulation/post-translational modification

Results in apoptosis of leukemia cells

[46]

Induction of autophagy

Transforms LC3-I to LC3-II; ↓ Bcl-2 and ↑ Bax expression

Induces autophagy, leading to apoptosis

[39, 40]

Inhibition of tumor cell viability and signaling pathway modulation

Inhibits NRF2/ARE pathway; ↓ cell viability, stimulates cytotoxicity in resistant cancer cell lines

Reduces viability and resistance in cancer cells

[24, 53, 63, 82]

Inhibition of angiogenesis

Disrupts MDM2-VEGF mRNA binding;

↓ MDM2/VEGF protein expression

Prevents angiogenesis, affecting tumor growth

[78]

Immunomodulatory effect

↑ HLA-I/II molecule expression; Enhances antigen presentation and immune response

Enhances immune-mediated recognition and elimination of cancer cells

[56, 80]