A novel role for 3, 4-dichloropropionanilide (DCPA) in the inhibition of prostate cancer cell migration, proliferation, and hypoxia-inducible factor 1alpha expression

We used Transwell assay to study cell migration, and used immunoblotting to study specific protein expression in the cells.In this report, we demonstrate that DCPA inhibited the migration and proliferation of DU145 and PC-3 prostate cancer cells induced by serum, insulin, and insulin-like growth factor I (IGF-I). We found that DCPA inhibited HIF-1 expression in a subunit-specific manner in these cancer cell lines induced by serum and growth factors, and decreased HIF-1α expression by affecting its protein stability.DCPA can inhibit prostate cancer cell migration, proliferation, and HIF-1α expression, suggesting that DCPA could be potentially used for therapeutic purpose for prostate cancer in the future.The genetic alterations in human cancer are a major focus of cancer research over the past two decades. Many genetic alterations such as activation of oncogenes and inactivation of tumor suppression genes lead to the increased expression of Hypoxia-inducible factor 1 (HIF-1) [1-4]. HIF-1 is a heterodimeric transcription factor composed of HIF-1α and HIF-1β subunits [5,6]. HIF-1 regulates the expression of many genes including vascular endothelial growth factor (VEGF), heme oxygenase 1, inducible nitric oxide synthase, aldolase, enolase, and lactate dehydrogenase A [7]. HIF-1 activity correlates with tumorigenesis and angiogenesis when wild type and HIF-1-deficient cell lines levels were injected into nude mice [1,8]. HIF-1 is overexpressed in many human cancers including prostate cancer [9]. HIF-1 expression in prostate cancer cells is induced by growth factors, and inhibited by phosphatidylinositol 3-kinase (PI3K) inhibitors and the tumor suppressor PTEN [2,10].The amide class compound, DCPA is a dichlorinated ring compound of low molecular weight. Previous investigations on the effects of this compound on lymphocyte and macrophage signaling pathways, reveal that this compound reduces NF-κB DNA binding ability [11]. This correlates with the down regulation of the pr