Extracellular ATP is a dynamic signaling molecule that modulates myriad of cellular functions through P2 purinergic receptors activation and is cytotoxic to a variety of cells at high concentration. But the mechanism of this extracellular ATP/ATP analogs- elicited cytotoxicity is not fully understood. In this study we aim to investigate whether there is differential sensitivity towards induction of apoptosis by ATP analogs (2’-Me ATP and 3’-Me ATP) and its effect on receptor mediated or extrinsic and mitochondria mediated or intrinsic apoptotic signaling pathways. Our findings demonstrated that the IC50 values for 2’-Me ATP and 3’-Me ATP were 3mM and 2mM, respectively, in Hep2, and SiHa cells. The downregulation of anti-apoptotic proteins Bcl-2 and Bcl-xL, along with a significant increase in the expression of the pro-apoptotic protein Bax (p<0.05), indicated the involvement of both pro- and anti-apoptotic factors in HeP2 cells, whereas in SiHa cells, a downregulation of anti-apoptotic proteins Bcl-2 and Bcl-xL was observed, whereas the expression level of the pro-apoptotic protein Bax remained unaffected. Furthermore, an upregulation of p53 and apoptosis-inducing factor (AIF) was observed in HeP2 cells (p<0.05) whereas, an upregulation of p53 was observed while no change was seen on the level of apoptosis inducing factor (AIF) was observed in SiHa cells. Additionally, there was a notable rise in caspase-3 and -9 activities, PARP cleavage, and the release of cytochrome c (p<0.05) from the mitochondria to the cytosol in both cells. Collectively, our study suggests that 3’-Me ATP induces apoptosis in Hep2 and SiHa cells through the intrinsic mitochondrial pathway.
Pathak, S. (2024). Induction of Apoptotic Signaling Pathways by 3’ methyl ATP in Different Malignant Cells: in vitro Study. Asian Pacific Journal of Cancer Prevention, 25(8), 2743-2750. doi: 10.31557/APJCP.2024.25.8.2743
MLA
Sujata Pathak. "Induction of Apoptotic Signaling Pathways by 3’ methyl ATP in Different Malignant Cells: in vitro Study". Asian Pacific Journal of Cancer Prevention, 25, 8, 2024, 2743-2750. doi: 10.31557/APJCP.2024.25.8.2743
HARVARD
Pathak, S. (2024). 'Induction of Apoptotic Signaling Pathways by 3’ methyl ATP in Different Malignant Cells: in vitro Study', Asian Pacific Journal of Cancer Prevention, 25(8), pp. 2743-2750. doi: 10.31557/APJCP.2024.25.8.2743
VANCOUVER
Pathak, S. Induction of Apoptotic Signaling Pathways by 3’ methyl ATP in Different Malignant Cells: in vitro Study. Asian Pacific Journal of Cancer Prevention, 2024; 25(8): 2743-2750. doi: 10.31557/APJCP.2024.25.8.2743
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