Regulatory Roles of Kaempferol on the PI3K/AKT/mTOR Signaling Pathway and Associated MicroRNAs in Different Cancer Types

Kaempferol, a naturally occurring dietary flavonoid abundantly found in various fruits and vegetables, has garnered significant attention due to its diverse pharmacological properties, most notably its potent anticancer activity. In the orchestration of cancer pathogenesis, the PTEN/PI3K/AKT/mTOR signaling cascade plays a pivotal role, where aberrant activation or dysregulation of this pathway drastically accelerates tumor cell proliferation, survival, and metabolic reprogramming, thereby driving tumorigenesis. Moreover, non-coding microRNAs (miRNAs) have emerged as key modulators involved in regulating this pathway, functioning as either oncogenes or tumor suppressors to determine cancer cell fate. Previous studies have demonstrated that kaempferol and its derivatives, owing to their molecular structures, suppress the PI3K/AKT/mTOR signaling pathway either directly or indirectly, thereby playing a critical role in inhibiting cancer cell proliferation. Hence, this comprehensive review elucidates the therapeutic potential of kaempferol and its derivatives, focusing specifically on their molecular mechanisms in modulating the PTEN/PI3K/AKT/mTOR pathway. Furthermore, this review highlights the crosstalk between kaempferol and the specific miRNAs targeting these signaling components in various cancer types.