Downregulation of c-Myc mediated ODC expression after purvalanol treatment is under control of upstream MAPK signaling axis in MCF-7 breast cancer cells

Abstract

IntroductionMammalian cell division, mitotic transfer of genome to new daughter cells, occurs when the cell has enough cytoplasmic content and DNA replication is finished correctly. The regulatory mechanisms during interphase (G1, S, G2 phases) control the cell division decision by the presence of various time-dependent and regularly activated molecules such as cyclin and cyclin-dependent kinases (CDKs) (Morgan et al., 1998). Each interphase phase has its own activated cyclin-CDK complexes that permit cell cycle progression during surveillance mechanisms (Arellano et al., 1997). Growth promoting signals due to growth factors change the cell cycle regulation and promote neoplastic transformation (Paulovich et al., 1997). Recently, new approaches to antineoplastic therapy are focused on cyclin-CDK complex inhibition.Thus far, 6 classes of chemical CDK inhibitors have been characterized, including purine-derived CDK inhibitors (Meijer, 1996). Olomoucine, roscovitine, and purvalanol are the most commonly investigated CDK inhibitors that cause cell cycle arrest and trigger apoptotic cell death. Roscovitine (CYC202, Seliciclib) or purvalanol induce apoptosis by causing cell cycle arrest in the G1 and G2/M phases in prostate (Ringer et al., 2010), lung (Zhang et al., 2010, multiple myeloma (Komina et al., 2011), colon, and breast cancer cell lines (Wesierska-Gadek et al., 2004;Arisan et al., 2012). Although CDK inhibitor-induced apoptotic cell death has been determined in breast cancer, the exact underlying molecular targets in cell death and survival mechanism have not been clarified yet.MAPKs are regulated by various cellular arrangements such as cell growth, differentiation, and apoptotic cell Abstract: Roscovitine and purvalanol are specific cyclin-dependent kinase (CDK) inhibitors, which induce apoptosis by triggering cell cycle arrest in various cancer cells such as colon, prostate, and breast cancer cells. Although the apoptotic action of roscovitine was clarified at the molecular level, the exact mechanism of purvalanol-induced apoptosis is still under investigation. The mitogenactivated protein kinase (MAPK) signaling cascade is activated by different inducers related to growth, proliferation, differentiation processes, or environmental stress factors. Recent reports showed that modulation of MAPKs might lead to regulation of c-Myc, which is a transcription factor for the polyamine (PA) biosynthesis enzyme, ornithine decarboxylase (ODC). PAs are amine-derived cationic molecules that play crucial roles in cell proliferation, growth, and differentiation. In this study, we investigated the potential role of the MAPK signaling cascade in the purvalanol-induced apoptosis mechanism by comparing the results of roscovitine in MCF-7 and MDA-MB-231 breast cancer cells. We found that CDK inhibitors decreased the cell viability in a dose-and time-dependent manner in MCF-7 and MDA-MB-231 cancer cells. Although both CDK inhibitors induced cell cycle arrest, which led to apoptosis by activating caspases and PARP cleavage in ...

S. cerevisiae β-glucan reduced viability of mouse hepatoma cells in vitro

“…The cell line of the murine hepatoma MH-22a was obtained from the Institute of Cytology, Russian Federation. The cultivation of the hepatoma cells was carried out under standard conditions: cells were grown in monolayer in the cell culture flasks in DMEM containing 10% fetal bovine serum and antibiotics at 37 °C (Shvenberger and Alexandrova, 2000;Grellier et al, 2008;Obakan et al, 2014).…”