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

Area of Science:

• Natural Products Chemistry
• Pharmacology
• Oncology

Background:

• Phloretin, a dihydrochalcone from fruits and vegetables, possesses antioxidant, antidiabetic, anti-inflammatory, and antitumor properties.
• It is abundant in apple tree leaves and Manchurian apricots.

Purpose of the Study:

• To review the anticancer potential of phloretin.
• To analyze its antiproliferative, proapoptotic, antimetastatic, and antiangiogenic activities in preclinical cancer models.
• To discuss its co-effects with conventional anticancer drugs.

Main Methods:

• Literature review of preclinical cancer models.
• Analysis of phloretin's effects on cellular signaling pathways, proteins (Bax, Bcl-2), caspases, MMPs, cytokines, and inflammatory enzymes.
• Evaluation of phloretin as a Pan-Assay Interference (PAIN) compound.

Main Results:

• Phloretin exhibits antiproliferative, proapoptotic, antimetastatic, and antiangiogenic activities in preclinical models.
• Its planar lipophilic polyphenol structure acts as a membrane-disrupting PAIN compound, potentially affecting cell-based assay validity.
• Phloretin non-specifically activates signaling pathways by reducing membrane dipole potential.

Conclusions:

• Phloretin demonstrates preclinical anticancer potential, warranting further investigation.
• Concerns regarding its PAIN compound status necessitate careful interpretation of cell-based activity data.
• Future research should focus on validating these findings and progressing towards clinical trials.