Phloretin, as a Potent Anticancer Compound: From Chemistry to Cellular Interactions

Abstract

Phloretin is a natural dihydrochalcone found in many fruits and vegetables, especially in apple tree leaves and the Manchurian apricots, exhibiting several therapeutic properties, such as antioxidant, antidiabetic, anti-inflammatory, and antitumor activities. In this review article, the diverse aspects of the anticancer potential of phloretin are addressed, presenting its antiproliferative, proapoptotic, antimetastatic, and antiangiogenic activities in many different preclinical cancer models. The fact that phloretin is a planar lipophilic polyphenol and, thus, a membrane-disrupting Pan-Assay Interference compound (PAIN) compromises the validity of the cell-based anticancer activities. Phloretin significantly reduces membrane dipole potential and, therefore, is expected to be able to activate a number of cellular signaling pathways in a non-specific way. In this way, the effects of this minor flavonoid on Bax and Bcl-2 proteins, caspases and MMPs, cytokines, and inflammatory enzymes are all analyzed in the current review. Moreover, besides the anticancer activities exerted by phloretin alone, its co-effects with conventional anticancer drugs are also under discussion. Therefore, this review presents a thorough overview of the preclinical anticancer potential of phloretin, allowing one to take the next steps in the development of novel drug candidates and move on to clinical trials.

Phloretin alleviates palmitic acid-induced oxidative stress in HUVEC cells by suppressing the expression of LncBAG6-AS

“…3D), which proved that the increase in MMP after interfering LncBAG6-AS was consistent with the reduction of the membrane potential by phloretin in our previous study. 12…”

“…3D), which proved that the increase in MMP after interfering LncBAG6-AS was consistent with the reduction of the membrane potential by phloretin in our previous study. 12 LncBAG6-AS regulates the transcription of downstream genes instead of adsorbing miRNAs Although LncBAG6-AS was shown to be involved in the regulation of OS, the molecular mechanism of LncBAG6-AS was further explored. It is known that the subcellular localization of lncRNA significantly impacted its function.…”

“…10 Phloretin [2′,4′,6′-trihydroxy-3-(4-hydroxyphenyl)-propiophenone] widely exists in juicy fruits and is famous for its biochemical activities, including antioxidant, anti-inflammatory, regulating metabolic homeostasis, and anti-cancer properties. [11][12][13] Regarding studies on phloretin in human umbilical vein endothelial cells (HUVECs), a commonly used VEC lines for CVD study, it was reported, as early as 1998, that phloretin effectively blocks both ascorbate (AA) and oxidized dehydroascorbate-stimulated assimilation of intracellular AA, thereby regulating glucose transport in HUVECs. 14 A further study found that phloretin could accelerate the lipid metabolism of hyperglycemic HUVECs and block atherosclerosis in STZ-induced diabetic mice by activating KLF2-eNOS.…”

Influence of scutellaria baicalensis extract on the thermo‐oxidative and composting stability of poly(butylene adipate‐co‐terephthalate)

“…Flavonoids and their glycosides are the main active ingredients, which have diversified effects, such as anti-tumor, anti-inflammatory, anti-aging, liver protection, and antioxidant. [44][45][46][47][48] Park et al 49 measured the total phenolic content (TPC) and antioxidant activity of SBE from different solvents and found a positive correlation between TPC and oxygen radical absorbance capacity. Han et al 50 identified that the bioactive components in scutellaria baicalensis are baicalein, visidulin III, and baicalin by LC-MS combined with a bioassay, showing strong free radical 2,2 0 -azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity.…”

“…So far, more than 40 chemical components have been identified in scutellaria baicalensis. Flavonoids and their glycosides are the main active ingredients, which have diversified effects, such as anti‐tumor, anti‐inflammatory, anti‐aging, liver protection, and antioxidant 44–48 . Park et al 49 measured the total phenolic content (TPC) and antioxidant activity of SBE from different solvents and found a positive correlation between TPC and oxygen radical absorbance capacity.…”