Eashana Arora

Background: Breast cancer is the second most common and fourth most fatal cancer worldwide with nearly 670,000 annual deaths.^1,2 Modifiable risk factors for breast cancer include obesity, alcohol consumption, and sedentary lifestyle.³ Decreased apoptosis and autophagy of tumor cells can lead to the pathogenesis of breast cancer progression.⁴ Omega-3 polyunsaturated fatty acids (n3-PUFAs) play an important role in cell membrane structure, fluidity, and cell signaling.⁵ The most abundant long chain n3-PUFAs are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).⁵ EPA and DHA have been recognized as potential dietary agents of breast cancer prevention via induction of apoptosis, autophagy, and cell cycle arrest. ⁵ EPA and DHA can conjugate with ethanolamine and dopamine to form n3-PUFA fatty acid derivatives.⁵ These derivatives are potential targets of exploration for effective therapy of breast cancer progression prevention.⁵

Objective: The purpose of this study is to understand the role and mechanism of n-3 PUFAs and n-3 PUFA derivatives in the treatment and prevention of breast cancer progression.

Search Methods: An online search of PubMed was conducted looking at sources from 2018-2024 using keywords such as “polyunsaturated fatty acids”, “n-3 PUFA derivatives”, “eicosapentaenoic acid”, “docosahexaenoic acid”, and “breast cancer”.

Results: A study indicated that dietary n3-PUFAs can regulate the tumor microenvironment and slow tumor growth.⁶ Mice fed a diet rich in n3-PUFAs showed slower tumor growth compared to mice fed an n6-PUFA rich diet.⁶ The next study reviewed the mechanism of the n3-PUFA amide derivatives in preventing the progression of breast cancer cells.⁷ The proposed mechanism of n-3 PUFA amide derivatives involves the activation of nuclear receptor PPARy, increasing expression of protein Beclin-1, and therefore increasing breast cancer cell autophagy and decreasing the cancer growth progression.⁵ The study demonstrated the proposed pro-autophagy mechanism of n3-PUFAs in human chondrocyte cells where the presence of DHA (an n3-PUFA) increased the expression of Beclin-1.⁷ The next study compared the effects of n3-PUFAs to n3-PUFA derivatives and demonstrated that lower concentrations of n3-PUFA derivatives are needed to inhibit breast cancer cell proliferation when compared to concentrations of n3-PUFAs.⁸ The final study observed the effect of n3-PUFAs in clinical studies and demonstrated that women consuming a diet high in n3-PUFAs showed improved intestinal barrier integrity compared to women consuming the control group diet.⁹ Improved intestinal barrier integrity is associated with decreased breast cancer progression.¹⁰

Conclusion: In conclusion, n3-PUFAs play a preventative role in breast cancer progression and slow mammary tumor growth. The mechanism of n3-PUFAs and n3-PUFAs derivatives involves increasing the expression of Beclin-1 and promoting autophagy. N3-PUFA derivatives show greater anticancer properties compared to EPA and DHA (n3-PUFAs). The preventative effects of n3-PUFAs and n3-PUFA derivatives in breast cancer progression are demonstrated in human studies. Increasing the understanding of the preventative role of n3-PUFAs and n3-PUFA derivatives in breast cancer progression can help further develop efficient therapeutic targets to improve patient outcomes via lifestyle changes.

Work Cited:

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