Abstract
The dramatic increase in the incidence of nonmelanoma skin cancer over the last
decades has been related to the augmented exposure to ultraviolet (UV) radiation
(UVR). It is known that apoptosis is induced as a protective mechanism after the
acute irradiation of keratinocytes, whereas apoptotic resistance and
carcinogenesis may follow the chronic exposure to UVR. We found that not all the
human keratinocytes lines studied underwent apoptosis following acute exposure to
UVR (10-60 mJ/cm(2)). Whereas UVR induced apoptosis in the HaCaT cells, NCTC 2544
and nr-HaCaT cells showed apoptosis resistance. The cytokeratin pattern of the
apoptosis-resistant cells indicated that they possessed a degree of
differentiation lower than that of HaCaT cells. They also showed an enhanced
expression of cyclooxygenase-2 (COX-2), an early marker of carcinogenesis in
various tissues, including skin. n-3 polyunsaturated fatty acids have drawn
increasing interest as nutritional factors with the potential to reduce UVR
carcinogenesis, and since they are apoptosis inducers and COX-2 inhibitors in
cancer cells, we investigated the ability of n-3 polyunsaturated fatty acids to
influence the resistance to UVR-induced apoptosis in keratinocytes. We observed
that docosahexaenoic acid (DHA) reverted the resistance of nr-HaCaT cells to
UVR-induced apoptosis, increasing the Bax/Bcl-2 ratio and caspase-3 activity, and
reduced COX-2 levels by inhibiting the expression of the human antigen R (HuR), a
known COX-2 mRNA stabilizer in keratinocytes. The transfection of nr-HaCaT cells
with HuR siRNA mimicked the proapoptotic effect of DHA. Overall, our findings
further support the role of DHA as a suitable anticarcinogenic factor against
nonmelanoma skin cancers.
Lingua originale | English |
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pagine (da-a) | 874-885 |
Numero di pagine | 12 |
Rivista | Journal of Nutritional Biochemistry |
Volume | 2011 |
Stato di pubblicazione | Pubblicato - 2010 |
Keywords
- COX-2
- HuR
- keratinocytes
- n-3 PUFA