- Title
- 5-Fluorouracil-induced apoptosis in colorectal cancer cells is caspase-9-dependent and mediated by activation of protein kinase C-d
- Creator
- Mhaidat, Nizar M.; Bouklihacene, Mohammed; Thorne, Rick F.
- Relation
- Oncology Letters Vol. 8, Issue 2, p. 699-704
- Publisher Link
- http://dx.doi.org/10.3892/ol.2014.2211
- Publisher
- Spandidos Publications
- Resource Type
- journal article
- Date
- 2014
- Description
- 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, PKCe 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 PKCd. The inhibition of PKCd was found to significantly inhibit 5-FU-induced apoptosis. These results indicated that 5-FU induces apoptosis in CRC by the activation of PKCd and caspase-9. In addition, the levels of PKCd activation may determine the sensitivity of CRC to 5-FU.
- Subject
- colorectal cancer; apoptosis; 5-fluorouracil; protein kinase C
- Identifier
- http://hdl.handle.net/1959.13/1066131
- Identifier
- uon:18028
- Identifier
- ISSN:1792-1074
- Language
- eng
- Full Text
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