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Saponin-Rich Extracts and Their Acid Hydrolysates Differentially Target Colorectal Cancer Metabolism in the Frame of
Marta Gómez de Cedrón1, Joaquín Navarro Del Hierro2,3, Marina Reguero1,4
1Precision Nutrition and Cancer Program, Molecular Oncology Group, IMDEA Food Institute, CEI UAM + CSIC, E-28049 Madrid, Spain.
Abstract:
Saponins or their aglycone form, sapogenin, have recently gained interest as bioactive agents due to their biological activities, their antitumoral effects being among them. Metabolic reprogramming has been recognized as a hallmark of cancer and, together with the increased aerobic glycolysis and glutaminolysis, the altered lipid metabolism is considered crucial to support cancer initiation and progression. The purpose of this study was to assess and compare the inhibitory effects on colorectal cancer cell lines of saponin-rich extracts from fenugreek and quinoa (FE and QE, respectively) and their hydrolyzed extracts as sapogenin-rich extracts (HFE and HQE, respectively). By mean of the latest technology in the analysis of cell bioenergetics, we demonstrate that FE and HFE diminished mitochondrial oxidative phosphorylation and aerobic glycolysis; meanwhile, quinoa extracts did not show relevant activities. Distinct molecular mechanisms were identified for fenugreek: FE inhibited the expression of TYMS1 and TK1, synergizing with the chemotherapeutic drug 5-fluorouracil (5-FU); meanwhile, HFE inhibited lipid metabolism targets, leading to diminished intracellular lipid content. The relevance of considering the coexisting compounds of the extracts or their hydrolysis transformation as innovative strategies to augment the therapeutic potential of the extracts, and the specific subgroup of patients where each extract would be more beneficial, are discussed in the frame of precision nutrition.
Insights
Fenugreek extracts, rich in saponins and sapogenins, show significant anti-colorectal cancer effects by inhibiting key metabolic pathways. These findings suggest potential for precision nutrition strategies in cancer therapy.
Area of Science:
- Nutritional Biochemistry
- Cancer Biology
- Pharmacology
Background:
- Saponins and sapogenins exhibit bioactive properties, including antitumoral effects.
- Metabolic reprogramming, altered lipid metabolism, aerobic glycolysis, and glutaminolysis are critical in cancer progression.
- Fenugreek and quinoa extracts are investigated for their potential against colorectal cancer.
Purpose of the Study:
- To evaluate and compare the colorectal cancer cell line inhibitory effects of saponin-rich fenugreek (FE) and quinoa (QE) extracts.
- To assess the effects of hydrolyzed extracts (HFE and HQE) as sapogenin-rich sources.
- To elucidate the molecular mechanisms underlying the observed anti-cancer activities.
Main Methods:
- Cell bioenergetics analysis using advanced technology.
- Assessment of mitochondrial oxidative phosphorylation and aerobic glycolysis.
- Gene expression analysis (TYMS1, TK1) and lipid metabolism target investigation.
Main Results:
- Fenugreek extracts (FE and HFE) significantly reduced mitochondrial oxidative phosphorylation and aerobic glycolysis.
- Quinoa extracts (QE and HQE) demonstrated no significant anti-cancer activity.
- FE inhibited TYMS1 and TK1 gene expression, enhancing 5-fluorouracil efficacy.
- HFE suppressed lipid metabolism, decreasing intracellular lipid content.
Conclusions:
- Fenugreek extracts, particularly FE and HFE, exhibit potent anti-colorectal cancer properties by targeting cellular metabolism.
- The study highlights the importance of considering extract composition and hydrolysis for therapeutic potential.
- Findings support the development of precision nutrition strategies for colorectal cancer treatment.
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