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.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Cambridge, MA 02139, USA.
authors.forename: Sasmit
authors.initials: S
authors.lastname: Sarangi
authors.forename: Ambarish
authors.initials: A
authors.lastname: Pandey
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Papa
authors.forename: Poulomi
authors.initials: P
authors.lastname: Sengupta
authors.forename: Jawahar
authors.initials: J
authors.lastname: Kopparam
authors.forename: Ushashi
authors.initials: U
authors.lastname: Dadwal
authors.forename: Sudipta
authors.initials: S
authors.lastname: Basu
authors.forename: Shiladitya
authors.initials: S
authors.lastname: Sengupta
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D058925:Receptors, Purinergic P2Y12 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D002945:Cisplatin