Gossypol is a lipid-soluble polyphenolic compound extracted from the cotton plant with antifertility, antioxidant, and anticancer properties [1]. Gossypol can block the release and utilization of ATP in sperm cells, reduce the contents of cytoskeleton and microtubule β-tubulin in spermatogenic cells and sperm cells, and inhibit the calcium influx in the cell membrane of sperm cells, as well as the activities of Mg-ATPase and Ca-Mg-ATPase[2]. Gossypol has been widely used to inhibit the proliferation of various tumor cells and induce mitochondrial dysfunction in cancer cells [3].
In vitro, Gossypol treatment for 12 hours significantly promoted the death of Jurkat cells overexpressing Bcl-2 and Jurkat cells overexpressing Bcl-XL, with IC50 values of 18.1µM and 22.9µM, respectively[4]. Treatment with 80 µM Gossypol for 24 hours significantly induced cell necrosis in U266 cells and enhanced the production of reactive oxygen species and DNA damage[5]. Treatment with 20µM Gossypol for 24 hours significantly induced apoptosis in H1975 cells and inhibited the phosphorylation of EGFR as well as the downstream signaling pathways[6].
In vivo, Gossypol treatment via intraperitoneal injection at a dose of 10mg/kg/day for 4 weeks significantly inhibited tumor growth in the MDA-MB-468 xenograft mouse model and reduced VEGF-mediated angiogenesis[7]. A single intraperitoneal injection of 40mg/kg of Gossypol for 8 hours significantly alleviated lung injury in mice induced by lipopolysaccharide (LPS) and inhibited the production of cytokines[8].
References:
[1] Keshmiri-Neghab H, Goliaei B. Therapeutic potential of gossypol: an overview[J]. Pharmaceutical Biology, 2014, 52(1): 124-128.
[2] Gadelha I C N, Fonseca N B S, Oloris S C S, et al. Gossypol toxicity from cottonseed products[J]. The Scientific World Journal, 2014, 2014(1): 231635.
[3] Paunovic D, Rajkovic J, Novakovic R, et al. The potential roles of gossypol as anticancer agent: Advances and future directions[J]. Chinese Medicine, 2023, 18(1): 163.
[4] Oliver C L, Miranda M B, Shangary S, et al. (−)-Gossypol acts directly on the mitochondria to overcome Bcl-2-and Bcl-XL-mediated apoptosis resistance[J]. Molecular cancer therapeutics, 2005, 4(1): 23-31.
[5] Xu R, Tian E, Tang H, et al. Proteomic analysis of gossypol induces necrosis in multiple myeloma cells[J]. BioMed Research International, 2014, 2014(1): 839232.
[6] Wang Y, Lai H, Fan X, et al. Gossypol inhibits non-small cell lung cancer cells proliferation by targeting EGFRL858R/T790M[J]. Frontiers in pharmacology, 2018, 9: 728.
[7] Xiong J, Li J, Yang Q, et al. Gossypol has anti-cancer effects by dual-targeting MDM2 and VEGF in human breast cancer[J]. Breast Cancer Research, 2017, 19(1): 27.
[8] Liu Z, Yang Z, Fu Y, et al. Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice[J]. Inflammation research, 2013, 62(5): 499-506.