Mediterranean Food Industry By-Products as a Novel Source of Phytochemicals with a Promising Role in Cancer Prevention

Abstract

The Mediterranean diet is recognized as a sustainable dietary approach with beneficial health effects. This is highly relevant, although the production of typical Mediterranean food, i.e., olive oil or wine, processed tomatoes and pomegranate products, generates significant amounts of waste. Ideally, this waste should be disposed in an appropriate, eco-friendly way. A number of scientific papers were published recently showing that these by-products can be exploited as a valuable source of biologically active components with health benefits, including anticancer effects. In this review, accordingly, we elaborate on such phytochemicals recovered from the food waste generated during the processing of vegetables and fruits, typical of the Mediterranean diet, with a focus on substances with anticancer activity. The molecular mechanisms of these phytochemicals, which might be included in supporting treatment and prevention of various types of cancer, are presented. The use of bioactive components from food waste may improve the economic feasibility and sustainability of the food processing industry in the Mediterranean region and can provide a new strategy to approach prevention of cancer.

Keywords: Mediterranean food industry; anticancer activity; by-products; cancer; polyphenols.

Figure 1

Characteristics of the Mediterranean diet and associated health benefits. The positive effects of the Mediterranean diet are also connected with specific effects on the microbiota composition.

Figure 2

Main bioactive compounds of different tomato fruit parts, namely, seeds, skin/peel and pulp. Quantitative data adapted from Kumar et al. [80].

Figure 3

Scheme of quercetin antitumor mechanisms of action. NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells)-iNOS (Inducible nitric oxide synthase)-COX2 (Cyclooxygenase 2) is an inflammatory signalling pathway which is blocked by quercetin induction in the tumour cell. It results in blockade of proliferation of tumour cells. Moreover, quercetin inhibits interaction of GRB (Growth factor receptor-bound protein), RhoA (Ras homolog family member A), SOS1 (Son of Sevenless 1) and RAS (Rat sarcoma virus), which prevents further metabolic reprograming. That includes inhibition of other metabolic molecules; PKC (Protein kinase C), MEKK-3, -7 (Mitogen-activated protein/ERK kinase -3, -7), JNK1/2 (c-Jun N-Terminal Protein Kinase 1/2), ERK1/2 (Extracellular signal-regulated kinase 1/2), p38 (Mitogen-activated protein kinase), PI3K (Phosphoinositide 3-kinase), IKKalpha/beta (Inhibitor of nuclear factor kappa-B kinase subunit beta) and, ultimately, further genetic transcription through MMP-2, -7, -8, and -9 (Matrix metalloproteinases). Finally, these events lead to tumour cell apoptosis.

Figure 4

Content of important bioactive compounds of the olive oil and olive oil by-products that can be further used in food industry and medical application [121].

Figure 5

Schematic overview of the most common signalling pathways through which flavonoids act on malignant processes in the cells. The final outcomes on the molecular level of cell organization include anti-proliferation, anti-inflammation, anti-metastasis and anti-angiogenesis effects. By acting upon p53 (cellular tumour antigen) molecule, which further acts on inhibiting cdc2 (Cyclin-dependent kinase) and CyclinB and therefore causes cell cycle arrest with anti-proliferation as an end result. Furthermore, p53 has an impact on blockading BH3 (borane trihydridoboron), BAX (BCL2 Associated X, Apoptosis Regulator) and Bcl-2 (B-cell lymphoma 2) molecules which leads to apoptosis and also causes inhibition of proliferation. Another significant molecule is MAPK (Mitogen-activated protein kinases), which further blocks the p38 (tumour suppressor), IKBalpha (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), NFkappaB (Nuclear factor kappa-light-chain-enhancer of activated B cells), COX2 (Cyclooxygenase) and PGH2/PGD2 (Prostaglandin H2/D2) pathway, with a final result of inhibition of inflammation. Another pathway on which flavonoids act upon is Akt (Protein kinase B, PKB)/FAK (Focal adhesion kinase)/Ras (Rat sarcoma virus protein)/PI3K (Phosphoinositide 3-kinases) pathway, through mTOR (mammalian target of rapamycin), FAK and MMP2/9 (matrix metallopeptidase 2/9) molecules. Blockade of Akt/FAK/Ras/PI3K pathway causes inhibition of metastasis. PI3K/Akt molecules are also significant in anti-proliferation module of flavonoid action, through another group of molecules, MAPK and ERK1 (Extracellular signal-regulated kinases)/JNK (c-Jun N-terminal kinases)/IP3 (Inositol trisphosphate). Finally, anti-angiogenesis properties that arise from flavonoid action is through Akt/NFkappaB pathway, which includes VEGF (Vascular endothelial growth factor), PI3K, ERK1/2, MAPK and STAT3 (Signal transducer and activator of transcription 3) molecules.