Investigation of the cytotoxic effect of flavopiridol in canine lymphoma cell lines

Abstract

The cyclin-dependent kinase (CDK) inhibitor, flavopiridol, was tested as a potential new cancer therapeutic agent to treat canine lymphoma by examining its effect on cell growth of canine lymphoma cell lines in vitro. Flavopiridol induced profound cell death in all eight lymphoma cell lines at 400 nM, and in all cases cell death was due to apoptosis. Apoptosis was inhibited by caspase inhibitor, despite the variable sensitivities between cell lines. Analysis of the mechanism of flavopiridol-induced apoptosis showed that Rb phosphorylation was inhibited, possibly due to CDK4 or CDK6 inhibition. There was also decreased expression of Rb protein and anti-apoptotic proteins, Mcl-1 and XIAP, possibly through transcriptional regulation by inhibition of CDK7 or CDK9 activation. Canine lymphoma cell line-xenotransplanted mice were then treated with flavopiridol and profound tumour shrinkage was observed. This study describes a new therapeutic approach using flavopiridol for canine lymphoma treatment.

Flavopiridol Strongly Sensitizes Canine Lymphoma Cells to TRAIL-induced Apoptosis

“…The possibility of using of FVP in veterinary oncology has also been explored. It was demonstrated that FVP at a concentration of 400 nM was able to induced apoptosis in many different canine lymphoma cell lines (CLBL-1, Ema, CL-1, GL-1, UL-1, CLGL90, Nody-1 and 17-71) (41). Accordingly, we found that CLBL-1 cells showed a remarkable sensitivity to FVP-induced cell death, being able to induce about 70% of dead cells after 24 h exposure at 200 nM, and around 30% when used at 100 nM.…”

“…Although the antitumor activity of FVP alone has already been explored in dogs (41), to our knowledge the combination of TRAIL with FVP has not yet been analyzed in canine tumors. Hence, we decided to examine the TRAILsensitizing activity of the aforementioned compound in canine lymphoma.…”