Uncovering the therapeutic potential of green pea waste in breast cancer: a multi-target approach utilizing LC-MS/MS metabolomics, molecular networking, and network pharmacology

• Published in: BMC complementary and alternative medicine 2024-10, Vol.24 (1), p.379-23, Article 379
• Main Authors: Khalil, Asmaa M, Sabry, Omar M, El-Askary, Hesham I, El Zalabani, Soheir M, Eltanany, Basma M, Pont, Laura, Benavente, Fernando, Mohamed, Ahmed F, Fayek, Nesrin M
• Format: Article
• Language: English
• Subjects: Adenosine; Agricultural wastes; Aldo-keto reductase; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents, Phytogenic - pharmacology; Antioxidants; Breast cancer; Breast Neoplasms - drug therapy; Carbohydrates; Care and treatment; Cell Line, Tumor; Chemical properties; Chromatography; Chromatography, Liquid; Cytotoxicity; Dietary minerals; Doxorubicin; Estrogen receptors; Estrogens; Female; Flavonoids; Food consumption; Food industry; Food plants; Food processing; Food waste; Green pea; Health aspects; Households; Humans; Ionization; LC-MS/MS metabolomics; Legumes; Liquid chromatography; Liquid Chromatography-Mass Spectrometry; Liquiritigenin; Mass spectrometry; Mass spectroscopy; Materia medica, Vegetable; MCF-7 Cells; Metabolites; Metabolomics; Methods; Molecular networking; Molecules; Natural products; Network Pharmacology; Networking; Open source software; p-Coumaric acid; Peas; Pharmacology; Pharmacology, Experimental; Phenolic acids; Phenols; Phytochemicals; Pisum sativum; Pisum sativum - chemistry; Plant extracts; Plant Extracts - chemistry; Plant Extracts - pharmacology; Protein-tyrosine-phosphatase; Proteins; Public domain; Quadrupoles; Receptors; Reductases; Scientific imaging; Seeds; Selectivity; Solvents; Tandem Mass Spectrometry; Tumor cell lines; Tyrosine; Waste valorization
• ISSN: 2662-7671; 2662-7671; 1472-6882
• DOI: 10.1186/s12906-024-04669-x

BACKGROUND PISUM SATIVUM: (PS) is a universal legume plant utilized for both human and animal consumption, particularly its seeds, known as green peas. The processing of PS in food industries and households produces a significant amount of waste that needs to be valorized. In this study, the metabolite profiles of the 70% ethanolic extracts of PS wastes, namely peels (PSP) and a combination of leaves and stems (PSLS), were investigated by liquid chromatography-electrospray ionization-quadrupole time-of-flight tandem mass spectrometry (LC-ESI-QTOF-MS/MS) followed by molecular networking. Different classes of metabolites were identified, being flavonoids and their derivatives, along with phenolic acids, the most abundant categories. Additionally, a comprehensive network pharmacology strategy was applied to elucidate potentially active metabolites, key targets, and the pathways involved in cytotoxic activity against breast cancer. This cytotoxic activity was investigated in MCF-7 and MCF-10a cell lines. Results revealed that PSLS extract exhibited a potent cytotoxic activity with a good selectivity index (IC 17.67 and selectivity index of 3.51), compared to the reference drug doxorubicin (IC 2.69 µg/mL and selectivity index of 5.28). Whereas PSP extract appeared to be less potent and selective (IC 32.92 µg/mL and selectivity index of 1.62). A similar performance was also observed for several polyphenolics isolated from the PSLS extract, including methyl cis p-coumarate, trans p-coumaric acid, and liquiritigenin/ 7-methyl liquiritigenin mixture. Methyl cis p-coumarate showed the most potent cytotoxic activity against MCF-7 cell line and the highest selectivity (IC 1.18 µg/mL (6.91 µM) and selectivity index of 27.42). The network pharmacology study revealed that the isolated compounds could interact with several breast cancer-associated protein targets including carbonic anhydrases 1, 2, 4, 9, and 12, as well as aldo-keto reductase family 1 member B1, adenosine A3 receptor, protein tyrosine phosphatase non-receptor type 1, and estrogen receptor 2. The uncovered therapeutic potential of PSLS and its metabolite constituents pave the way for an efficient and mindful PS waste valorization, calling for further in-vitro and in-vivo research.