New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways.
Alma MartelliMarzieh OmraniMaryam ZarghooniValentina CitiSimone BrogiVincenzo CalderoneAntoni Sureda GomilaShahrokh LorzadehSimone C da Silva RosaBeniamin Oscar GrabarekRafał StaszkiewiczMarek Jan ŁosSeyed Fazel NabaviSeyed Mohammad NabaviParvaneh MehrbodDaniel J KlionskySaeid GhavmiPublished in: Cancers (2022)
Macroautophagy (autophagy) has been a highly conserved process throughout evolution and allows cells to degrade aggregated/misfolded proteins, dysfunctional or superfluous organelles and damaged macromolecules, in order to recycle them for biosynthetic and/or energetic purposes to preserve cellular homeostasis and health. Changes in autophagy are indeed correlated with several pathological disorders such as neurodegenerative and cardiovascular diseases, infections, cancer and inflammatory diseases. Conversely, autophagy controls both apoptosis and the unfolded protein response (UPR) in the cells. Therefore, any changes in the autophagy pathway will affect both the UPR and apoptosis. Recent evidence has shown that several natural products can modulate (induce or inhibit) the autophagy pathway. Natural products may target different regulatory components of the autophagy pathway, including specific kinases or phosphatases. In this review, we evaluated ~100 natural compounds and plant species and their impact on different types of cancers via the autophagy pathway. We also discuss the impact of these compounds on the UPR and apoptosis via the autophagy pathway. A multitude of preclinical findings have shown the function of botanicals in regulating cell autophagy and its potential impact on cancer therapy; however, the number of related clinical trials to date remains low. In this regard, further pre-clinical and clinical studies are warranted to better clarify the utility of natural compounds and their modulatory effects on autophagy, as fine-tuning of autophagy could be translated into therapeutic applications for several cancers.
Keyphrases
- endoplasmic reticulum stress
- cell death
- induced apoptosis
- oxidative stress
- cell cycle arrest
- signaling pathway
- clinical trial
- cancer therapy
- cardiovascular disease
- public health
- healthcare
- transcription factor
- randomized controlled trial
- type diabetes
- drug delivery
- cell therapy
- mental health
- pi k akt
- binding protein
- lymph node metastasis
- phase ii