Inhibition of S6K1 enhances dichloroacetate-induced cell death was written by Hong, Sung-Eun;Shin, Keong-Sub;Lee, Yun-Han;Seo, Sung-Kum;Yun, Sun-Mi;Choe, Tae-Boo;Kim, Hyun-Ah;Kim, Eun-Kyu;Noh, Woo Chul;Kim, Jong-Il;Hwang, Chang-Sun;Lee, Jin Kyung;Hwang, Sang-Gu;Jin, Hyeon-Ok;Park, In-Chul. And the article was included in Journal of Cancer Research and Clinical Oncology in 2015.Recommanded Product: 1255517-76-0 This article mentions the following:
Purpose: The unique metabolic profile of cancer (aerobic glycolysis) is an attractive therapeutic target for cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, has been shown to reverse glycolytic phenotype and induce mitochondrion-dependent apoptosis. In the present study, we investigated the effects of S6 kinase 1 (S6K1) inhibition on DCA-induced cell death and the underlying mechanisms in breast cancer cells. Methods: Cell death was evaluated by annexin V and PI staining. The synergistic effects of DCA and PF4708671 were assessed by isobologram anal. Small interfering RNA (siRNA) was used for suppressing gene expression. The mRNA and protein levels were measured by RT-PCR and Western blot anal., resp. Results: PF4708671, a selective inhibitor of S6K1, and knockdown of S6K1 with specific siRNA enhanced DCA-induced cell death. Interestingly, a combination of DCA/PF4708671 markedly reduced protein expression of a glycolytic enzyme, hexokinase 2 (HK2). Suppression of HK2 activity using specific siRNA and 2-deoxyglucose (2-DG) further enhanced cell sensitivity to DCA/PF4708671. Overexpression of Myc-tagged HK2 rescued cell death induced by DCA/PF4708671. Conclusions: Based on these findings, we propose that inhibition of S6K1, in combination with the glycolytic inhibitor, DCA, provides effective cancer therapy. In the experiment, the researchers used many compounds, for example, 2-((4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl)methyl)-6-(trifluoromethyl)-1H-benzo[d]imidazole (cas: 1255517-76-0Recommanded Product: 1255517-76-0).
2-((4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl)methyl)-6-(trifluoromethyl)-1H-benzo[d]imidazole (cas: 1255517-76-0) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Recommanded Product: 1255517-76-0
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Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics