The “Yin and Yang” of Natural Compounds in Anticancer Therapy of Triple-Negative Breast Cancers

Abstract

Among the different types of breast cancers, triple-negative breast cancers (TNBCs) are highly aggressive, do not respond to conventional hormonal/human epidermal growth factor receptor 2 (HER2)-targeted interventions due to the lack of the respective receptor targets, have chances of early recurrence, metastasize, tend to be more invasive in nature, and develop drug resistance. The global burden of TNBCs is increasing regardless of the number of cytotoxic drugs being introduced into the market each year as they have only moderate efficacy and/or unforeseen side effects. Therefore, the demand for more efficient therapeutic interventions, with reduced side effects, for the treatment of TNBCs is rising. While some plant metabolites/derivatives actually induce the risk of cancers, many plant-derived active principles have gained attention as efficient anticancer agents against TNBCs, with fewer adverse side effects. Here we discuss the possible oncogenic molecular pathways in TNBCs and how the purified plant-derived natural compounds specifically target and modulate the genes and/or proteins involved in these aberrant pathways to exhibit their anticancer potential. We have linked the anticancer potential of plant-derived natural compounds (luteolin, chalcones, piperine, deguelin, quercetin, rutin, fisetin, curcumin, resveratrol, and others) to their ability to target multiple dysregulated signaling pathways (such as the Wnt/β-catenin, Notch, NF-κB, PI3K/Akt/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK) and Hedgehog) leading to suppression of cell growth, proliferation, migration, inflammation, angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, and activation of apoptosis in TNBCs. Plant-derived compounds in combination with classical chemotherapeutic agents were more efficient in the treatment of TNBCs, possibly with lesser side effects.

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

“…The multifaceted ability of metformin to influence cancer cell growth and cancer progression through various molecular mechanisms, as discussed above, has made it an interesting candidate drug with potential in the treatment of breast cancer. In the following sections of the article, we briefly discuss the cellular, pre-clinical, and clinical studies that are currently testing metformin as a monotherapy or in combination with other chemotherapeutic drugs or phytochemicals/natural compounds for its efficacy as an anti-cancer/anti-tumor agent in the treatment of estrogen receptor (ER) positive, progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER2) positive types of breast cancers, and triple negative breast cancers (TNBCs) [135].…”

Antifungal, Antitumoral and Antioxidant Potential of the Danube Delta Nymphaea alba Extracts

“…Most active natural biological products are secondary metabolites with complex structures [10], and among them, compounds such as flavonoids, isoprenoids and alkaloids extracted from plants have been exploited for various illnesses due to their pharmacological properties [11], accounting for more than 30% of total antineoplastic drugs [12]. Polyphenols as gallic acid, ellagic acid, and flavonoids such as quercetin and apigenin contribute to antioxidant activity [13,14], and they have gained importance as cytotoxic agents, also promoting apoptosis in cancer cells [15,16].…”

Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression

“…Several studies emphasize the central role of angiogenesis in BC development and confirm the prominent role of angiogenesis in human invasive BC [12]. Breast cancers which are classified based on the hormone receptor status and molecular profile [169] have differentially regulated miRNA profiles [170]. The miRNA profile of different subtypes of BC show clear correlation with the clinicopathological factors such as grade, stage, Tp53 status and vascular invasion [170].…”