Diacerein retards cell growth of chondrosarcoma cells at the G2/M cell cycle checkpoint via cyclin B1/CDK1 and CDK2 downregulation

Abstract

BackgroundChondrosarcoma is characterized for its lack of response to conventional cytotoxic chemotherapy, propensity for developing lung metastases, and low rates of survival. Research within the field of development and expansion of new treatment options for unresectable or metastatic diseases is of particular priority. Diacerein, a symptomatic slow acting drug in osteoarthritis (SYSADOA), implicates a therapeutic benefit for the treatment of chondrosarcoma by an antitumor activity.MethodsAfter treatment with diacerein the growth behaviour of the cells was analyzed with the xCELLigence system and MTS assay. Cell cycle was examined using flow cytometric analysis, RT-PCR, and western blot analysis of specific checkpoint regulators. The status for phosophorylation of mitogen-activated protein kinases (MAPKs) was analyzed with a proteome profiler assay. In addition, the possible impact of diacerein on apoptosis was investigated using cleaved caspase 3 and Annexin V/PI flow cytometric analysis.ResultsDiacerein decreased the cell viability and the cell proliferation in two different chondrosarcoma cell lines in a dose dependent manner. Flow cytometric analysis showed a classical G2/M arrest. mRNA and protein analysis revealed that diacerein induced a down-regulation of the cyclin B1-CDK1 complex and a reduction in CDK2 expression. Furthermore, diacerein treatment increased the phosphorylation of p38α and p38β MAPKs, and Akt1, Akt2, and Akt 3 in SW-1353, whereas in Cal-78 the opposite effect has been demonstrated. These observations accordingly to our cell cycle flow cytometric analysis and protein expression data may explain the G2/M phase arrest. In addition, no apoptotic induction after diacerein treatment, neither in the Cal-78 nor in the SW-1353 cell line was observed.ConclusionsOur results demonstrate for the first time that the SYSADOA diacerein decreased the viability of human chondrosarcoma cells and induces G2/M cell cycle arrest by CDK1/cyclin B1 down-regulation.

Chronic Carrageenan Toxicity and the Possible Ameliorative Role of Diacerein in Experimental Animals

“…Expression of the proliferative marker (PCNA) in thyroid significantly increased after diacerin administration in this present research, and these results are in contrary with Lohberger et al (2015), who suggested that diacerein has anti-proliferative activities. Their research discussed the action of diacerein on tumor cells.…”

Long Non-Coding RNA Expression Profiles for the Characterization of Different Bladder Cancer Grade

“…LUCAT1 got a higher clustering coefficient with CCNB1 both in two groups. Other studies indicated that LUCAT1and CCNB1 play important roles in the biological processes, such as cell cycle, DNA damage response and cell apoptosis [35][36][37]. At the same time, TRANRIC web site also indicates there are some connections between LUCAT1 and CCNB1.…”

Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways

“…The CDK inhibitor p21 inhibits the cyclin/CDK complex and promotes cell cycle arrest in response to various stimuli [22]. Additionally, it has been reported that cyclin B1 expression is associated with G2/M cell cycle progression [21,23]. To explore the mechanisms by which Shikonin induced a G2/M phase arrest in A375 cells, proteins related to cell cycle regulation were assessed using western blot analysis.…”