The p90rsk-mediated signaling of ethanol-induced cell proliferation in HepG2 cell line

Abstract

Ribosomal S6 kinase is a family of serine/threonine protein kinases involved in the regulation of cell viability. There are two subfamilies of ribosomal s6 kinase, (p90rsk, p70rsk). Especially, p90rsk is known to be an important downstream kinase of p44/42 MAPK. We investigated the role of p90rsk on ethanol-induced cell proliferation of HepG2 cells. HepG2 cells were treated with 10~50 mM of ethanol with or without ERK and p90rsk inhibitors. Cell viability was measured by MTT assay. The expression of pERK1, NHE1 was measured by Western blots. The phosphorylation of p90rsk was measured by ELISA kits. The expression of Bcl-2 was measured by qRT-PCR. When the cells were treated with 10~30 mM of ethanol for 24 hour, it showed significant increase in cell viability versus control group. Besides, 10~30 mM of ethanol induced increased expression of pERK1, p-p90rsk, NHE1 and Bcl-2. Moreover treatment of p90rsk inhibitor attenuated the ethanol-induced increase in cell viability and NHE1 and Bcl-2 expression. In summary, these results suggest that p90rsk, a downstream kinase of ERK, plays a stimulatory role on ethanol-induced hepatocellular carcinoma progression by activating anti-apoptotic factor Bcl-2 and NHE1 known to regulate cell survival.

Expressional and Functional Characterization of Intracellular pH Regulators and Effects of Ethanol in Human Oral Epidermoid Carcinoma Cells

“…Because an acidic pH condition induce growth arrest or cell death [55], thus change of any one of these H + -equivalent transporters may play a significant role in the progression of carcinogenesis of oral cancer. Recently, Kim et al have reported that ethanol (10~30 mM) induces cell proliferation of HepG2 cells, activates NHE1 and anti-apopotitc Bcl-2 through enhancing the activities of ERK1 and p90rsk, and the maximum effects are shown at the concentration of 20 mM both [22]. Also, in our present study, the similar trend of ethanol (10~30 mM) on NHE1 expression has been found (Fig.…”

“…NHE and NBC [23,41]. Moreover, it has been shown that ethanol treatment (10~30 mM) induced cell proliferation mainly by increasing the activities of ERK1 and p90rsk in HepG2 cells, and the maximum effects were shown at the concentration of 20 mM both [22]. However, the related knowledge of ethanol on pH i regulators is none in OEC-M1 cells.…”

“…7). Indeed, p90rsk, hyperactive NHE1 even at the resting pH and the resulting cellular alkalinization have been reported to be directly related to uncontrolled proliferation in malignancy cells [22]. Thus, p90rsk that regulates cellular proliferation, as well as NHE1, may be an important molecule for therapeutic targeting in ethanol-induced carcinoma progression.…”

“…Some of the Bcl-2 family proteins [19] and endonucleases [20] have been identified to be sensitive to apoptosis related early intracellular alkalinization [21]. Moreover, treatment with p90rsk inhibitor has been found to reduce the ethanol-induced increase in viability of cell and expression of NHE1 and Bcl-2 in hepatocellular carcinoma [22].…”

Effects of Andrographolide on Intracellular pH Regulation, Cellular Migration, and Apoptosis in Human Cervical Cancer Cells (Running Tittle: Effects of Andrographolide on pH Regulators and Apoptosis in Cervical Cancer)

“…Some of the Bcl-2 family proteins [20] and endonucleases [21] have been identified as pH sensitive during early intracellular alkalinization in apoptosis [22]. Moreover, treatment with p90rsk inhibitor has been found to reduce the ethanol-induced increase in viability of cells and expression of Na + /H + exchanger isoform 1 (NHE1) and Bcl-2 in hepatocellular carcinoma [23]. However, the related knowledge of transmembrane pH i regulators is still not clear in human normal endocervical cells (End1), human normal ectocervical cells (Ect1), and in human cervical cancer cells (HeLa).…”