Abstract
Simple SummaryColorectal cancer remains the second leading cause of cancer-related death worldwide, which is a situation that requires the continuous search for natural bioactive compounds that can mitigate its effects or can be used as co-adjuvants in the frame of precision nutrition. The elucidation of the mechanisms underlying the bioenergetics of colorectal tumorous cells as well as the modulation of lipid metabolism-related genes may greatly contribute to personalized therapies. We show that saponin- and sapogenin-rich extracts from fenugreek are able to strongly inhibit colorectal cancer cells’ growth, which is related to a reduction in the mitochondrial oxidative phosphorylation and the inhibition of aerobic glycolysis, in which each of the extracts target the molecular pathways related to lipid metabolism in a different manner. We propose that this outcome may have important implications on their potential use against colon cancer in the context of precision nutrition.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.
Highlights
Cancer is a complex and heterogeneous disease where genetic and environmental factors contribute to initiation, progression, and resistance to treatments
The cytotoxicity of the saponin-rich extract from fenugreek is superior than its acid-hydrolyzed form, which is probably due to synergisms with other bioactive compounds contained in the extract
It has been demonstrated that the cytotoxic effects of these extracts on Colorectal cancer (CRC) cells may be related to alterations in the energetic metabolism of the cells, to a reduction in their mitochondrial oxidative phosphorylation and to the inhibition of their aerobic glycolysis
Summary
Cancer is a complex and heterogeneous disease where genetic and environmental factors contribute to initiation, progression, and resistance to treatments. Metabolic reprogramming has been recognized as a hallmark of cancer [1,2]. In recent years, alterations in lipid metabolism have been identified as key factors in cancer [2,3,4]. Genetic alterations are the most studied factors, environmental factors including those related to lifestyle contribute to the onset and progression of cancer. The World Health Organization (WHO) estimates that up to one-third of all cancers could be prevented through lifestyle changes, such as diet. In the case of gastric tumors, this percentage rises to more than half, constituting the main factor in their development [5]. Colorectal cancer (CRC) is the second most prevalent type of cancer in the world, and its appearance is closely associated to obesity and metabolic syndrome
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