P2Y12 receptor inhibition augments cytotoxic effects of cisplatin in breast cancer

Sasmit Sarangi; Ambarish Pandey; Anne Laure Papa; Poulomi Sengupta; Jawahar Kopparam; Ushashi Dadwal; Sudipta Basu; Shiladitya Sengupta

doi:10.1007/s12032-013-0567-y

P2Y12 receptor inhibition augments cytotoxic effects of cisplatin in breast cancer

Sasmit Sarangi, Ambarish Pandey, Anne Laure Papa, Poulomi Sengupta, Jawahar Kopparam, Ushashi Dadwal, Sudipta Basu, Shiladitya Sengupta

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21 Scopus citations

Abstract

Expression of P2Y12 receptors has been documented in some cancer cell lines like C6 glioma, renal carcinoma and colon carcinoma. However, its direct role in altering response to chemotherapeutics has not been studied. In this study, we characterize the expression of P2Y12 receptor in breast cancer cell lines and evaluate its role in enhancing the cytotoxic effects of cisplatin. We observed a significant upregulation in P2Y12 expression in 4T1 breast cancer cell line with cisplatin treatment. Co-administration of P2Y12 inhibitor with cisplatin resulted in significantly higher cytotoxic response in 4T1 cancer cell line. This was mediated by HIF1α-dependent upregulation of cellular apoptotic pathways. These findings identify P2Y12 receptor as a potential target to enhance antitumor efficacy of chemotherapeutic agents like cisplatin.

Original language	English (US)
Article number	567
Journal	Medical Oncology
Volume	30
Issue number	2
DOIs	https://doi.org/10.1007/s12032-013-0567-y
State	Published - Jun 2013

Keywords

Breast cancer
Cisplatin
HIF1α
P2Y12 receptor

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1007/s12032-013-0567-y

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title = "P2Y12 receptor inhibition augments cytotoxic effects of cisplatin in breast cancer",

abstract = "Expression of P2Y12 receptors has been documented in some cancer cell lines like C6 glioma, renal carcinoma and colon carcinoma. However, its direct role in altering response to chemotherapeutics has not been studied. In this study, we characterize the expression of P2Y12 receptor in breast cancer cell lines and evaluate its role in enhancing the cytotoxic effects of cisplatin. We observed a significant upregulation in P2Y12 expression in 4T1 breast cancer cell line with cisplatin treatment. Co-administration of P2Y12 inhibitor with cisplatin resulted in significantly higher cytotoxic response in 4T1 cancer cell line. This was mediated by HIF1α-dependent upregulation of cellular apoptotic pathways. These findings identify P2Y12 receptor as a potential target to enhance antitumor efficacy of chemotherapeutic agents like cisplatin.",

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AU - Sarangi, Sasmit

AU - Pandey, Ambarish

AU - Papa, Anne Laure

AU - Sengupta, Poulomi

AU - Kopparam, Jawahar

AU - Dadwal, Ushashi

AU - Basu, Sudipta

AU - Sengupta, Shiladitya

PY - 2013/6

Y1 - 2013/6

N2 - Expression of P2Y12 receptors has been documented in some cancer cell lines like C6 glioma, renal carcinoma and colon carcinoma. However, its direct role in altering response to chemotherapeutics has not been studied. In this study, we characterize the expression of P2Y12 receptor in breast cancer cell lines and evaluate its role in enhancing the cytotoxic effects of cisplatin. We observed a significant upregulation in P2Y12 expression in 4T1 breast cancer cell line with cisplatin treatment. Co-administration of P2Y12 inhibitor with cisplatin resulted in significantly higher cytotoxic response in 4T1 cancer cell line. This was mediated by HIF1α-dependent upregulation of cellular apoptotic pathways. These findings identify P2Y12 receptor as a potential target to enhance antitumor efficacy of chemotherapeutic agents like cisplatin.

AB - Expression of P2Y12 receptors has been documented in some cancer cell lines like C6 glioma, renal carcinoma and colon carcinoma. However, its direct role in altering response to chemotherapeutics has not been studied. In this study, we characterize the expression of P2Y12 receptor in breast cancer cell lines and evaluate its role in enhancing the cytotoxic effects of cisplatin. We observed a significant upregulation in P2Y12 expression in 4T1 breast cancer cell line with cisplatin treatment. Co-administration of P2Y12 inhibitor with cisplatin resulted in significantly higher cytotoxic response in 4T1 cancer cell line. This was mediated by HIF1α-dependent upregulation of cellular apoptotic pathways. These findings identify P2Y12 receptor as a potential target to enhance antitumor efficacy of chemotherapeutic agents like cisplatin.

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KW - Cisplatin

KW - HIF1α

KW - P2Y12 receptor

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P2Y12 receptor inhibition augments cytotoxic effects of cisplatin in breast cancer

Abstract

Keywords

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