Involvement of oncogenic tyrosine kinase NPM-ALK in trifluoperazine-induced cell cycle arrest and apoptosis in ALK+ anaplastic large cell lymphoma

Hematology
Linlin HuPing Shi

Abstract

Trifluoperazine (TFP) has potential anticancer activity that was demonstrated in different types of cancer cells. However, little is known about its effects in the T-cell ALK+ anaplastic large cell lymphoma (ALCL). In this study, we investigated the effects of TFP in this aggressive type of cancer. The cytotoxicities of TFP on DEL and SUP-M2 cells were measured by trypan blue staining. The effects of TFP on cell cycle and apoptosis in DEL and SUP-M2 cells were determined by flow cytometry. The underlying anticancer mechanism of TFP was investigated by real-time PCR, Western Blotting, and nucleophosmin-ALK (NPM-ALK) tyrosine kinase assay in DEL cells. Our results show that TFP did not significantly affect cell viability of human normal lymphocytes, whereas it reduced the cell viability of the ALK+ T-cell lymphoma cells, DEL and SUP-M2, in concentration- and time-dependent manners. TFP also induced cell cycle arrest at G0/G1 phase, and caused cell apoptosis in these cells. These effects could be explained by the involvement of NPM-ALK and its downstream cell survival regulatory proteins. Our results demonstrate for the first time that TFP is capable of inducing degradation and inhibition of kinase activity of NPM-ALK, as well as ...Continue Reading

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