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

Mhaidat,Nizar  M.; Bouklihacene,Mohammed; Thorne,Rick   F.

doi:10.3892/ol.2014.2211

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

Authors:
- Nizar M. Mhaidat
- Mohammed Bouklihacene
- Rick F. Thorne
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Affiliations: Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan, Department of Cancer Research Unit, Newcastle University, Newcastle, NSW 2300, Australia
Published online on: June 2, 2014 https://doi.org/10.3892/ol.2014.2211
Pages: 699-704

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Abstract

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, PKCε 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.

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