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.
Gossypol是一种从棉花植株中提取的脂溶性多酚类化合物，具有抗生育、抗氧化和抗癌特性[1]。Gossypol可阻断精子细胞中ATP的释放和利用，降低生精细胞和精子细胞中细胞骨架及微管蛋白β-微管蛋白的含量，并抑制精子细胞膜上的钙离子内流以及Mg-ATP酶和Ca-Mg-ATP酶的活性[2]。Gossypol已被广泛用于抑制多种肿瘤细胞的增殖，并诱导癌细胞的线粒体功能障碍[3]。
在体外，Gossypol处理12小时显著促进了过表达Bcl-2的Jurkat细胞和过表达Bcl-XL的Jurkat细胞的死亡，IC50值分别为18.1µM和22.9µM[4]。80µM的Gossypol处理U266细胞24小时，显著诱导了细胞坏死，并增强了活性氧的产生和DNA损伤[5]。20µM的Gossypol处理H1975细胞24小时，显著诱导了细胞凋亡，并抑制了EGFR的磷酸化及下游信号通路[6]。
在体内，每日腹腔注射10mg/kg剂量的Gossypol，持续4周，显著抑制了MDA-MB-468异种移植小鼠模型中的肿瘤生长，并减少了VEGF介导的血管生成[7]。单次腹腔注射40mg/kg的Gossypol，作用8小时，显著减轻了脂多糖（LPS）诱导的小鼠肺损伤，并抑制了细胞因子的产生[8]。