Evaluation of anticancer potency of Cu-isatin-1-(2-pyridyl) piperazine thiosemicarbazone (Cu-Istpypz) against epidermoid carcinoma cell line (A431)
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...
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Elsevier
2025-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715624006891 |
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| author | Indranil Banerjee Piyush Kumar Narendra K. Singh Paras N. Yadav Yuba Raj Pokharel |
| author_facet | Indranil Banerjee Piyush Kumar Narendra K. Singh Paras N. Yadav Yuba Raj Pokharel |
| author_sort | Indranil Banerjee |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-301c4630382744479199bb8235a3293b |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Results in Chemistry |
| spelling | doaj-art-301c4630382744479199bb8235a3293b2025-01-29T05:00:50ZengElsevierResults in Chemistry2211-71562025-01-0113101993Evaluation of anticancer potency of Cu-isatin-1-(2-pyridyl) piperazine thiosemicarbazone (Cu-Istpypz) against epidermoid carcinoma cell line (A431)Indranil Banerjee0Piyush Kumar1Narendra K. Singh2Paras N. Yadav3Yuba Raj Pokharel4Faculty of Life Science and Biotechnology, South Asian University, Rajpur Road, Maidan Garhi, New Delhi 110068, IndiaFaculty of Life Science and Biotechnology, South Asian University, Rajpur Road, Maidan Garhi, New Delhi 110068, IndiaDepartment of Chemistry, Amrit Campus, Tribhuvan University, Kathmandu, NepalCentral Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu, Nepal; Corresponding authors.Faculty of Life Science and Biotechnology, South Asian University, Rajpur Road, Maidan Garhi, New Delhi 110068, India; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2211715624006891ApoptosisA431CaspaseCell viabilityClonogenicDNA fragmentation |
| spellingShingle | Indranil Banerjee Piyush Kumar Narendra K. Singh Paras N. Yadav Yuba Raj Pokharel Evaluation of anticancer potency of Cu-isatin-1-(2-pyridyl) piperazine thiosemicarbazone (Cu-Istpypz) against epidermoid carcinoma cell line (A431) Results in Chemistry Apoptosis A431 Caspase Cell viability Clonogenic DNA fragmentation |
| title | Evaluation of anticancer potency of Cu-isatin-1-(2-pyridyl) piperazine thiosemicarbazone (Cu-Istpypz) against epidermoid carcinoma cell line (A431) |
| title_full | Evaluation of anticancer potency of Cu-isatin-1-(2-pyridyl) piperazine thiosemicarbazone (Cu-Istpypz) against epidermoid carcinoma cell line (A431) |
| title_fullStr | Evaluation of anticancer potency of Cu-isatin-1-(2-pyridyl) piperazine thiosemicarbazone (Cu-Istpypz) against epidermoid carcinoma cell line (A431) |
| title_full_unstemmed | Evaluation of anticancer potency of Cu-isatin-1-(2-pyridyl) piperazine thiosemicarbazone (Cu-Istpypz) against epidermoid carcinoma cell line (A431) |
| title_short | Evaluation of anticancer potency of Cu-isatin-1-(2-pyridyl) piperazine thiosemicarbazone (Cu-Istpypz) against epidermoid carcinoma cell line (A431) |
| title_sort | evaluation of anticancer potency of cu isatin 1 2 pyridyl piperazine thiosemicarbazone cu istpypz against epidermoid carcinoma cell line a431 |
| topic | Apoptosis A431 Caspase Cell viability Clonogenic DNA fragmentation |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624006891 |
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