Pentoxifylline induces caspase-dependent apoptosis in colorectal cancer cells

Colorectal cancer is a leading cause of mortality worldwide. Resistance of this cancer to the available chemotherapeutic agents creates a need to develop new therapeutic agents. Pentoxifylline (PTX) has been shown to have anticancer effects on multiple cancer types. In this study, we evaluated the anticancer effect of PTX in CRC cells. We measured PTX's effect on cell proliferation using the MTT assay and on cell death induction by PI staining/flowcytometry. We also assessed the effect of treatment on mitochondrial membrane potential (MMP). We found that PTX arrested the growth SW480 CRC cells with a peak effect plateauing at 10 mM of PTX after 72 hrs of treatment. Surprisingly, similar effect wasn't noticed in HCT-116 cells. Similar pattern of effect was noticed on apoptosis of both cell lines, as PTX induced more apoptosis on SW480 cells with no similar effect on HCT-116 cells. Studies using variable caspase inhibitors showed involvement of primarily capsase-9, as well as caspases-2 and -3 but not capsase-8. PTX also induced MMP changes leading to caspase-dependent apoptotic cell death. In addition to that, results indicated that apoptosis was caspase-dependent and was mediated through the mitochondria. These findings indicate that PTX has a promising antitumor activity against CRC cells and warrants further clinical evaluation.