Induction of apoptosis and cell cycle arrest on u266 multiple myeloma cell line by prochlorperazine

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Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Bilimleri Enstitüsü, Fen Bilimleri Enstitüsü, Türkiye

Tezin Onay Tarihi: 2016

Öğrenci: HEPŞEN HAZAL HÜSNÜGİL

Eş Danışman: CAN ÖZEN, SREEPARNA BANERJEE

Özet:

Multiple myeloma (MM) is a plasma cell neoplasm accounting for 1% of all malignancies and 13% of hematological malignancies. Despite the introduction of potent anticancer agents, MM remains as an incurable disease. High frequency of relapses and acquisition of resistance to current chemotherapy create a need for the development of novel agents for MM treatment. Prochlorperazine (PCP) is an FDA-approved phenothiazine drug, mainly used for the treatment of chemotherapy-associated nausea and vomiting. In addition, PCP was studied as a potent antitumor agent on various cancers such as melanoma, glioblastoma, colon and breast cancers. The aim of this study was to investigate the anticancer effect and mechanism of PCP on U266 MM cell line. We first studied the anticancer potential of PCP on U266 cell line at various doses and time points. Next, three flow cytometric apoptosis assays; JC-1, Caspase 3 and PE Annexin V-7 AAD were performed. PCP’s effect on cell cycle was examined with propidium iodide staining. As a part of the study, anticancer potential of cisplatin-PCP combination was also investigated. vi PCP exhibited dose- and time-dependent inhibitory effect on U266 cell viability. IC50 of PCP was calculated as 21.8 ± 0.8 µM. It was demonstrated that PCP exerted cytotoxic action through inducing apoptosis. No change in mitochondrial membrane potential was observed with JC-1 MMP assay which suggested activation of extrinsic apoptotic pathways by PCP. Cell cycle analysis indicated that exposure of U266 cells to PCP resulted in cell cycle arrest at G2/M phase. It was also demonstrated that PCP-cisplatin combination exhibited additive effect. These results indicated that PCP has potent anticancer activity alone and in combination with cisplatin on U266 MM cells. Further in-depth mechanistic studies and in vivo experiments are warranted to evaluate its therapeutic potential