Evaluation of Anticancer Potency of Cu-Isatin-1-(2-Pyridylpiperazine) Thiosemicarbazone (Cu-Istpypz) Against Epidermoid Carcinoma Cell Line (A431)

• DOI: 10.2139/ssrn.4925558
• Publication Date: 2024-08-19T15:50:28Z
• Authors: Yuba Raj Pokharel; Indranil Banerjee; Narendra Kumar S...; Paras Nath Yadav; Piyush Kumar
• Keywords: Isatin; Semicarbazone; Epidermoid carcinoma

A series of Isatin thiosemicarbazones and their copper(II) complexes were synthesized and evaluated for their anti-cancer activities to develop potent chemotherapeutic agents. Among the compounds synthesized, copper conjugated isatin-thiosemicarbazone derivative, Cu-Istpypz, showed considerable anti-proliferative activity against A431 (Skin Cancer) and A549 (Lung Cancer) cell lines. Cell viability assay using crystal violet dye exhibited the effects of the compounds against those cell lines. Cu-Istpypz was highly effective in inhibiting A431 cell proliferation at lower concentrations. The compound Cu-Istpypz also suppressed the colony formation of A431 cells in a concentration-dependent manner, as demonstrated by the clonogenic assay. Additionally, at higher concentrations, Cu-Istpypz slowed down the migration and wound-healing capabilities of A431 cells. RT-PCR and western blot analysis indicated that the compound induced the expression of pro-apoptotic Bax and inhibited anti-apoptotic Bcl-2 and Bcl-xl in a concentration-dependent manner. Further, the compound induces intrinsic apoptosis in A431 cells by activating the JNK signalling pathway and suppressing the PI3K/AKT pathway. DNA fragmentation assay further confirms the onset of apoptosis in the presence of the compound. All these confirm that Cu-Istpypz thiosemicarbazone has the potential to be developed as a future chemotherapeutic agent in the treatment of skin cancer.