Cancer Glycolytic Dependence as a New Target of Olive Leaf Extract

Abstract

Oleuropein (Ole), the main bioactive phenolic component of Olea europaea L. has recently attracted the scientific attention for its several beneficial properties, including its anticancer effects. This study is intended to investigate whether an olive leaf extract enriched in Ole (OLEO) may counteract the aerobic glycolysis exploited by tumor cells. We found that OLEO decreased melanoma cell proliferation and motility. OLEO was also able to reduce the rate of glycolysis of human melanoma cells without affecting oxidative phosphorylation. This reduction was associated with a significant decrease of glucose transporter-1, protein kinase isoform M2 and monocarboxylate transporter-4 expression, possible drivers of such glycolysis inhibition. Extending the study to other tumor histotypes, we observed that the metabolic effects of OLEO are not confined to melanoma, but also confirmed in colon carcinoma, breast cancer and chronic myeloid leukemia. In conclusion, OLEO represents a natural product effective in reducing the glycolytic metabolism of different tumor types, revealing an extended metabolic inhibitory activity that may be well suited in a complementary anti-cancer therapy.

Potential Uses of Olive Oil Secoiridoids for the Prevention and Treatment of Cancer: A Narrative Review of Preclinical Studies

“…Experimental evidence has proven that exposure to an olive leaf extract enriched in oleuropein reduced proliferation and motility in different cancer cells, such as melanoma [ 112 ], colon carcinoma [ 113 ], breast cancer [ 114 ] and chronic myeloid leukemia [ 115 ]. These effects are due to metabolic inhibitory activity exerted by oleuropein that neutralizes the aerobic glycolysis exploited by tumor cells, revealing that it may be effectively used as a complementary anti-cancer therapy [ 112 ].…”

Phytochemicals Block Glucose Utilization and Lipid Synthesis to Counteract Metabolic Reprogramming in Cancer Cells

“…A recent study demonstrated that oleuropein could significantly reduce the viability of breast cancer cells, suggesting its potential as a promising herbal medication to treat cancers [111]. Another report revealed the activity of oleuropein in reducing the expression of GLUT1 and PKM2 in the glycolysis pathway, although the mechanism underlying this regulation was not elucidated [112]. Menendez et al reported that polyphenols, flavonoids and secoiridoids extracted from olive oil could significantly suppress FASN protein levels in HER2-overexpressing breast cancer cells, including HER2 gene-amplified SKBR3 cells and engineered HER2-overexpressing MCF-7 cells.…”

Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approches in Non Communicable Diseases

“…The beneficial effects of EVOO is the result of the combination of functional components, such as fatty acid composition (with a high content of oleic acid) and wide minor bioactive constituents, among which polyphenols such as oleuropein from Olea europaea L. Several biological properties attributed to oleuropein, providing beneficial effects in the prevention of degenerative diseases, are mainly based on its antioxidant potential [12], but a recent review by Nediani et al [2] describes how oleuropein has multi-target activity including the anti-inflammatory [13], the anti-amyloid aggregation [14], anti-hypertensive [15], hypoglycemic [16], cardioprotective [17], autophagy inducer [18,19] and anticancer [20], also in combination with standard anti-cancer drugs [21]. In this context, the anti-proliferative and pro-apoptosis activity of oleuropein, in addition to its ability to reduce the glycolytic metabolism of different tumor types [22], it might represent an effective tool for complementary cancer therapy. Due to these biological and biomedical effects of oleuropein, special attention is devoted to the recovery, recycling, and upgrading of food waste, leaves and by-products for its use in agronomic, nutraceutical, and biomedical applications [23].…”