Department of Chemical Science and Technology, University of Rome "Tor Vergata", 00133 Rome, Italy.
Ph.D. Course in Microbiology, Immunology, Infectious Diseases, and Transplants (MIMIT), University of Rome "Tor Vergata", 00133 Rome, Italy.
Molecules. 2023 May 2;28(9):3856. doi: 10.3390/molecules28093856.
Metal-derived platinum complexes are widely used to treat solid tumors. However, systemic toxicity and tumor resistance to these drugs encourage further research into similarly effective compounds. Among others, organotin compounds have been shown to inhibit cell growth and induce cell death and autophagy. Nevertheless, the impact of the ligand structure and mechanisms involved in the toxicity of organotin compounds have not been clarified. In the present study, the biological activities of commercially available bis(tributyltin) oxide and tributyltin chloride, in comparison to those of specially synthesized tributyltin trifluoroacetate (TBT-OCOCF) and of cisplatin, were assessed using cells with different levels of tumorigenicity. The results show that tributyltins were more cytotoxic than cisplatin in all the tested cell lines. NMR revealed that this was not related to the interaction with DNA but to the inhibition of glucose uptake into the cells. Moreover, highly tumorigenic cells were less susceptible than nontumorigenic cells to the nonunique pattern of death induced by TBT-OCOCF. Nevertheless, tumorigenic cells became sensitive when cotreated with wortmannin and TBT-OCOCF, although no concomitant induction of autophagy by the compound was detected. Thus, TBT-OCOCF might be the prototype of a family of potential anticancer agents.
金属衍生的铂配合物被广泛用于治疗实体瘤。然而，这些药物的全身毒性和肿瘤耐药性促使人们进一步研究类似有效的化合物。在其他化合物中，有机锡化合物已被证明能抑制细胞生长并诱导细胞死亡和自噬。然而，配体结构和涉及有机锡化合物毒性的机制尚未阐明。在本研究中，使用具有不同致瘤性水平的细胞评估了市售的双（三丁基锡）氧化物和三丁基氯化锡与专门合成的三丁基锡三氟乙酸酯（TBT-OCOCF）和顺铂的生物活性。结果表明，在所有测试的细胞系中，三丁基锡比顺铂的细胞毒性更强。NMR 表明，这与与 DNA 的相互作用无关，而是与葡萄糖摄取到细胞中的抑制有关。此外，高度致瘤性细胞比非致瘤性细胞对 TBT-OCOCF 诱导的非独特死亡模式的敏感性较低。然而，当用渥曼青霉素和 TBT-OCOCF 共同处理时，致瘤性细胞变得敏感，尽管未检测到该化合物同时诱导自噬。因此，TBT-OCOCF 可能是一类潜在抗癌药物的原型。
