Heliyon, 2019., Aug 9;5(8):e02251. doi: 10.1016/j.heliyon.2019.e02251.

Treatment with flaxseed oil induces apoptosis in cultured malignant cells.

Buckner AL Buckner CA Montaut S Lafrenie RM

Abstract

Flaxseed oil is widely recognized for its exceptional nutritional value, high concentration of fiber-based lignans and large amounts of ω-fatty acids. It is one of a generic group of functional foods that is often taken by cancer patients as a potential treatment. We have examined the anti-cancer effects of flaxseed oil by studying its direct effects on cancer cell growth in vitro. Treatment of a variety of cancer cell lines with flaxseed oil decreased their growth in a dose-dependent manner while non-malignant cell lines showed small increases in cell growth. Cells treated with a mixture of fatty acids, including α-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid and lignans including enterodiol and enterolactone was also able to decrease the growth of cancer cells. Treatment of B16-BL6 murine melanoma and MCF-7 breast cancer cells with flaxseed oil induced apoptosis as determined by changes in cell morphology, annexin V staining, DNA fragmentation and/or caspase activation. In addition, treatment with flaxseed oil also disrupted mitochondrial function in B16-BL6 and MCF-7 cells. These results indicate that flaxseed oil can specifically inhibit cancer cell growth and induce apoptosis in some cancer cells and suggests it has further potential in anti-cancer therapy.

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Key Points

This study showed that treatment with flaxseed oil can inhibit the growth of cultured malignant cells including breast cancer cells, cervical cancer cells, leukemia cells, and melanoma cells in a dose-dependent manner. However, the growth of non-malignant cells was not inhibited by treatment with flaxseed oil. Since flaxseed oil preferentially kills malignant cells it may be a potential component of cancer care. Treatment of B16-BL6 mouse melanoma cells and MCF-7 breast cancer cells with flaxseed oil was able to induce apoptosis in a dose- and time-dependent manner.

The results also showed that treatment with flaxseed oil or a combination of individual fatty acids including α-linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, linoleic acid, oleic acid, and palmitic acid and the lignans enterodiol and enterolactone decreased labelling of mitochondria with MitoTracker Red which is consistent with a collapse in mitochondrial membrane potential (Δψ) as shown by others in response to flaxseed or α-linolenic acid treatment. Treatment with sunflower oil did not affect mitochondria labelling and lysosomal labelling with Lysotracker Red was not significantly blocked by either flaxseed or sunflower oil. The effect of flaxseed oil on mitochondrial function would be consistent with activation of endogenous apoptotic pathways although further studies are required to demonstrate this linkage. The fact that direct presentation of flaxseed oil in media was able to affect cell proliferation suggests either that the oil contains the specific dietary active component or that the cancer cells themselves are able to metabolize the oil to create the active agent. Studies to examine the impact of flaxseed oil treatment of cultured cells on membrane lipid composition are underway.