Research: SAM and COLLEAGUES,

Listed in Issue 272

Abstract

SAM and COLLEAGUES, 1. a Department of Cellular and Molecular Biotechnology , Institute of Biotechnology, Urmia University , Urmia , Iran; 2. b National Cell Bank of Iran , Pasteur Institute of Iran , Tehran , Iran investigated alterations of p53 and survivin expression and induction of apoptosis in DHA-treated Molt-4 cells that serve as a model for acute lymphoblastic leukemia (ALL) cells.

Background

In acute lymphoblastic leukemia (ALL), resistance to chemotherapy is associated with inactivation of p53 and upregulation of survivin. Thus, targeting the p53 and survivin expression may provide an attractive strategy for ALL treatment. It has been shown that fish-oil-derived docosahexaenoic acid (DHA) activates several anti-tumorigenic mechanisms in tumour cells, but little is known regarding the role of DHA on modulating p53 and survivin expression in ALL cells.

Methodology

In this study, we investigated the alterations of the p53 and survivin expression and induction of apoptosis in DHA-treated Molt-4 cells that serve as a model for ALL cells. Molt-4 cells were treated with 50, 100, 150, and 200 μM DHA after which cell proliferation, survivin mRNA and protein levels, p53 protein level, caspase-3 activation, and apoptotic rates were evaluated by different cellular and molecular techniques.

Results

After 48- and 72-h treatments with DHA at concentrations ranging from 50 to 200 μM, cell proliferation rates were measured to be 80.5-44.4%, and 73.4-14.4%, respectively, compared to untreated cells. We also found that treatment for 48 h with 200 μM DHA resulted in 10.8- and 3.6-fold increase in p53 protein level and caspase-3 activation followed by 4.7-and 1.6-fold decrease in survivin mRNA and protein levels, respectively, compared to untreated cells. Treatment of cells with different concentrations of DHA dramatically increased the p53/survivin and caspase-3/survivin ratios by 2.8- to 16.9-fold and 3.3 to 5.6-fold increases, respectively, compared to untreated cells. A decrease in the number of cells ranging from 16% to 70% and an increase in the number of apoptotic cells ranging from 9.3% to 93% was also observed with increasing DHA concentrations.

Conclusion

In conclusion, p53 and survivin may provide promising targets of DHA in ALL cells and this compound with high proapoptotic capacity represents the possibility of its therapeutic application for ALL treatment.

References

Sam MR1, Esmaeillou M1, Shokrgozar MA2. Fish-Oil-Derived DHA-mediated Enhancement of Apoptosis in Acute Lymphoblastic Leukemia Cells is Associated with Accumulation of p53, Downregulation of Survivin, and Caspase-3 Activation. Nutr Cancer. 69(1):64-73. doi: 10.1080/01635581.2017.1247884. Epub Nov 23 2016. Jan 2017.

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