5-Fluorouracil-induced apoptosis in colorectal cancer cells is caspase-9-dependent and mediated by activation of protein kinase C-δ

• Published in: Oncology letters 2014-08, Vol.8 (2), p.699-704
• Main Authors: MHAIDAT, NIZAR M, BOUKLIHACENE, MOHAMMED, THORNE, RICK F
• Format: Article
• Language: English
• Subjects: 5-fluorouracil; Analysis; Apoptosis; Cancer therapies; Chemotherapy; Colorectal cancer; Drug therapy; Enzymes; Fluorouracil; Genetic aspects; Health aspects; Immunoglobulins; Kinases; Oncology; Phosphorylation; Physiological aspects; protein kinase C; Protein kinases; Proteins; Response rates; Studies
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2014.2211

Elucidation of the molecular mechanisms by which 5-fluorouracil (5-FU) induces apoptosis is required in order to understand the resistance of colorectal cancer (CRC) cells to 5-FU. In the current study, 5-FU-induced apoptosis was assessed using the propidium iodide method. Involvement of protein kinase C (PKC) was assessed by evaluating the extent of their activation in CRC, following treatment with 5-FU, using biochemical inhibitors and western blot analysis. The results revealed that 5-FU induces varying degrees of apoptosis in CRC cells; HCT116 cells were identified to be the most sensitive cells and SW480 were the least sensitive. In addition, 5-FU-induced apoptosis was caspase-dependent as it appeared to be initiated by caspase-9. Furthermore, PKCɛ was marginally expressed in CRC cells and no changes were observed in the levels of cleavage or phosphorylation following treatment with 5-FU. The treatment of HCT116 cells with 5-FU increased the expression, phosphorylation and cleavage of PKCδ. The inhibition of PKCδ was found to significantly inhibit 5-FU-induced apoptosis. These results indicated that 5-FU induces apoptosis in CRC by the activation of PKCδ and caspase-9. In addition, the levels of PKCδ activation may determine the sensitivity of CRC to 5-FU.