2. Academic Validation
  3. Metabolic Shift Induced by ω -3 PUFAs and Rapamycin Lead to Cancer Cell Death

Metabolic Shift Induced by ω -3 PUFAs and Rapamycin Lead to Cancer Cell Death

  • Cell Physiol Biochem. 2018;48(6):2318-2336. doi: 10.1159/000492648.
Shenglong Zhu 1 2,  Ninghan Feng 1 3,  Guangxiao Lin 2,  Yuelin Tong 2,  Xuan Jiang 2,  Qin Yang 1 2,  Shunhe Wang 2,  Wei Chen 2,  Zhao He 1 2 4 5,  Yong Q Chen 1 2 6
Affiliations

Affiliations

  • 1 Wuxi Medical School, Jiangnan University, Wuxi, China.
  • 2 State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China.
  • 3 The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Nanjing, China.
  • 4 Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.
  • 5 Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China.
  • 6 School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
PMID: 30114709 DOI: 10.1159/000492648
Abstract

Background/aims: Rapamycin (Rp), the main mammalian target of rapamycin complex inhibitor, is a promising therapeutic agent for breast Cancer. However, metabolic disorders and drug resistance reduce its efficacy. Epidemiological, clinical, and experimental studies have demonstrated that omega-3 polyunsaturated fatty acids (ω-3 PUFAs) significantly reduce the incidence and mortality of breast Cancer and improve metabolic disorders.

Methods: Three breast Cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Rp plus ω-3 PUFA treatment. The production of Reactive Oxygen Species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics, seahorse experiments, and western blot analysis.

Results: We found that ω-3 PUFAs and Rp synergistically induced cell cycle arrest and Apoptosis in vitro and in vivo, accompanied by Autophagy blockage. In addition, Rp-induced hypertriglyceridemia and hypercholesterolemia were completely abolished by ω-3 PUFA supplementation. Moreover, the combined treatment of ω-3 PUFA and Rp significantly inhibited glycolysis and glutamine metabolism. The anti-tumor effects of this combination treatment were dependent on ROS production, which was increased by β-oxidation and Oxidative Phosphorylation.

Conclusion: Our study revealed that ω-3 PUFA enhanced the anti-tumor activity of Rp while minimizing its side effects in vitro and in vivo. These results provide novel insights into the mechanisms underlying the potential beneficial effects of Rp combined with ω-3 PUFAs on the prevention of breast Cancer.

Keywords

Breast cancer; Cancer metabolism; Rapamycin; ω-3 PUFAs.

Figures
Products