Docosahexanoic acid induces dose dependent cell death in an early undifferentiated subtype of acute myeloid leukemia cell line

Abstract

Acute myeloid leukemia (AML) is the most frequently diagnosed adulthood leukemia, yet current therapies offer a cure rate of less than 30%. This may be due in part to the fact that the leukemia-initiating cells in AML reside within the rare and highly primitive CD34+CD38- hematopoietic stem/progenitor cell (HSC) population that are often resistant to chemotherapy. Docosahexanoic acid (DHA), a major component of fish oil, has previously been shown to inhibit the induction and progression of breast, prostate and colon cancer, and increase the therapeutic effects of numerous chemotherapeutics, often by enhancing apoptosis. In the present studies, we investigated DHA's effect on the primitive and undifferentiated AML cell line KG1a, to explore the potential of this fatty acid to serve as adjuvant therapy for AML. Treatment of KG1a cells with DHA for 96 hours did not lead to maturation or cell cycle modification when compared to an untreated KG1a control (n = 4). However, DHA treatment of KG1a cells resulted in a progressive loss of viability, DNA fragmentation, and an increase in Annexin V expression, demonstrating DHA-induced apoptosis (n = 4). Moreover, expression of the pro-apoptotic protein Bax was increased, with resultant skewing in the Bax/bcl-2 ratio, providing a mechanistic explanation for the observed DHA-induced increase in apoptosis. Since we also show that DHA does not have a detrimental effect on normal hematopoiesis our results suggest that DHA could potentially serve as an well-tolerated adjuvant in the treatment of AML patients.

DHA is a more potent inhibitor of breast cancer metastasis to bone and related osteolysis than EPA

“…Recently, a number of studies show that ω-3 FA, especially DHA, can act as an excellent adjuvant to enhance the effect of various drugs [59–61]. It has been reported that tumor cells can be made more sensitive to chemotherapy than non-tumor cells when membrane lipids are enriched with DHA [62].…”

Omega-3 polyunsaturated fatty acids and cancer: lessons learned from clinical trials

“…In this case, DHA was effective on the primitive and undifferentiated AML cell line KG1a. In this model, DHA induced DNA fragmentation with an increase in the expression of the pro-apoptotic protein Bax [138].…”

The Multifaceted Effects of Omega-3 Polyunsaturated Fatty Acids on the Hallmarks of Cancer

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