Superior role for p53 in DNA breakage compared with parthanatos by tumor microenvironment of breast cancer cells
Subject Areas : Developmental biology of plants and animals , development and differentiation in microorganisms
شهرزاد چیتگران
1
,
شادی ربیعی
2
,
محمود براتی
3
,
پریسا حیات
4
,
سید عبدالحمید انگجی
5
,
شیما توکل
6
1 -
2 -
3 -
4 -
5 -
6 -
Keywords:
Abstract :
Background: Cells are continuously exposed to various cellular stresses. Over 50% of human cancers carry mutations in the p53 gene, therefore p53 has been considered a critical tumor suppressor. Upon DNA damage, p53 accumulates in the cellular nucleus through post-translational modifications.
Method and materials: In this study, the impact of an acidic and conditioned MDA-MBA231 breast cancer environment on the pathways of apoptosis and parthanatos in normal fibroblast cells was examined. The expression of Bcl2, Bax genes involved in apoptosis, PARP1, PARG genes involved in parthanatos, and p53 protein was evaluated. Moreover, the electrophoresis method was used to study DNA breakage in normal, acidic, conditioned, and acidic plus conditioned media.
Results: The results showed that the level of DNA damage in acidic and conditioned media was less than that in conditioned media and higher than that in normal and acidic media. Although conditioned media induced less Bax and Bax/Bcl2 ratio than other media in fibroblasts, there was no significant difference between the Bax/Bcl2 ratio in other groups as the apoptosis index. PARP1 and PARG gene levels were the lowest in conditioned plus acidic media, and p53 was downregulated in conditioned media.
Conclusion: Parthanatos and the level of Bax were not responsible for DNA damage in conditioned media, whereas a decrease in p53 was partly associated with poor DNA repair under stress conditions in cancer cells in normal fibroblasts.
