In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700 026, West Bengal, India; Department of Chemistry, Rammohan College, 102/1, Raja Rammohan Sarani, College Street, Kolkata, West Bengal 700009, India.
In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700 026, West Bengal, India.
Environ Toxicol Pharmacol. 2017 Dec;56:383-392. doi: 10.1016/j.etap.2017.11.004. Epub 2017 Nov 6.
Cancer chemotherapy suffers from selectivity and undesired toxicity of the drugs. Since zinc is a biocompatible tracer element and cysteine derivatives are used in cancer chemoprevention, we intend to develop a complex of zinc and cysteine-derivatives as potent, non-toxic anticancer agents. Herein, we synthesized and characterized cysteine based ligand, 2-[(2-Hydroxy-3-methoxy-benzylidene)-amino]-3-mercapto-propionic acid and its Zn-complex, which are found to be non-toxic towards normal human PBMC. Data also revealed that only Zn-complex exhibited remarkable apoptosis in drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 cancer cells as assessed by MTT, Cell cycle and AnnexinV binding assay. Moreover, Zn-complex altered ROS and GSH level of the respective cell lines. Finally, treatment of Zn-complex in Swiss albino mice did not show any systemic toxicity in preliminary trials in normal mice and remarkably increased the life-span of EAC bearing mice. In conclusion, the synthesized Zn-complex may be developed for efficacious, multidrug resistance reversal, non-toxic chemotherapeutic agents in future.
癌症化疗存在药物选择性和非期望毒性的问题。由于锌是一种生物相容性示踪元素，半胱氨酸衍生物被用于癌症化学预防，我们旨在开发一种锌和半胱氨酸衍生物的复合物作为有效、无毒的抗癌药物。在此，我们合成并表征了基于半胱氨酸的配体 2-[(2-羟基-3-甲氧基-亚苄基)-氨基]-3-巯基-丙酸及其锌配合物，发现它们对正常人外周血单核细胞（PBMC）无毒。数据还表明，只有锌配合物在 CCRF-CEM 敏感型和 CEM/ADR5000 多药耐药型癌细胞中通过 MTT、细胞周期和 AnnexinV 结合试验显示出显著的凋亡作用。此外，锌配合物改变了相应细胞系的 ROS 和 GSH 水平。最后，在正常小鼠的初步试验中，锌配合物在瑞士白化小鼠中的治疗并未显示出任何全身毒性，并显著延长了荷瘤 EAC 小鼠的寿命。总之，合成的锌配合物可能在未来被开发为有效、多药耐药逆转、无毒的化疗药物。
