التفاصيل البيبلوغرافية
| العنوان: |
Violacein induces apoptosis in human breast cancer cells through up regulation of BAX, p53 and down regulation of MDM2. |
| المؤلفون: |
Alshatwi, Ali A., Subash-Babu, P., Antonisamy, P. |
| المصدر: |
Experimental & Toxicologic Pathology; Jan2016, Vol. 68 Issue 1, p89-97, 9p |
| مصطلحات موضوعية: |
VIOLACEIN, APOPTOSIS, BREAST cancer, P53 antioncogene, BAX protein, DOWNREGULATION |
| مستخلص: |
We aimed to explore the anticancer potential of violacein and its time, dose dependent mechanism of action in human MCF-7 breast cancer cells. We observed, violacein inhibit MCF-7 cells viability in a time and dose-dependent manner, IC 50 value was 4.5 μM in 24 h, 1.7 μM in 48 h and 0.51 μM in 72 h. Violacein triggered generation of intra cellular ROS even from the lower doses, significant ROS production was observed from 0.25, 0.45 μM dose range and it is relative to higher doses. Further we fixed 0.45 μM and 4.5 μM as an experimental dose for relative dose dependent analysis. In nuclear staining, after 48 h 0.45 μM dose showed characteristic apoptotic morphological changes such as, 59% of cells in apoptosis and 11% of cells in necrotic stage, also in 72 h we found 68% in apoptosis and 12% in necrotic stage. However, 4.5 μM (IC 50 ) dose of violacein, 78% of cells became apoptotic and 21% in necrotic after 48 h; but in 72 h only 61% cells are in apoptotic, necrosis was increased to 38%. Violacein increased both mitochondrial and extra mitochondrial apoptotic pathway related gene expressions; it was confirmed by increased CYP1A, GPX, GSK3β and TNF-α gene. Further, 0.45 and 4.5 μM of violacein increased apoptotic genes, such as Bax, p53, caspase 3, Fas, FADD and markedly reduced Bcl-2 and MDM2 expression levels to two fold when compared to control. In addition violacein upregulated poly ADP-ribose polymerase (PARP), CDKN1A and caspase-9 significantly ( p ≤ 0.05) when compared to control. Relative quantification of caspase-8 was differently expressed; there were no changes in 0.45 μM, but in 4.5 μM we found two fold increased caspase-8 expression. In conclusion, lower dose of violacein treatment induced apoptosis in human breast cancer MCF-7 cells through TNF-α and p53 dependent mitochondrial pathways. [ABSTRACT FROM AUTHOR] |
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