Plant natural compounds: targeting pathways of autophagy as anti-cancer therapeutic agents

Abstract

Natural compounds derived from plant sources are well characterized as possessing a wide variety of remarkable anti-tumour properties, for example modulating programmed cell death, primarily referring to apoptosis, and autophagy. Distinct from apoptosis, autophagy (an evolutionarily conserved, multi-step lysosomal degradation process in which a cell destroys long-lived proteins and damaged organelles) may play crucial regulatory roles in many pathological processes, most notably in cancer. In this review, we focus on highlighting several representative plant natural compounds such as curcumin, resveratrol, paclitaxel, oridonin, quercetin and plant lectin - that may lead to cancer cell death - for regulation of some core autophagic pathways, involved in Ras-Raf signalling, Beclin-1 interactome, BCR-ABL, PI3KCI/Akt/mTOR, FOXO1 signalling and p53. Taken together, these findings would provide a new perspective for exploiting more plant natural compounds as potential novel anti-tumour drugs, by targeting the pathways of autophagy, for future cancer therapeutics.

Figure 1

Stages of the process of autophagy. Autophagy can be stimulated by nutrient deprivation, hypoxia, cytokine activity, hormone activity and DNA damage. (a) Induction requires Atg 1 and Atg13, which in turn can be inhibited by mTOR. (b) Vesicle nucleation depends on Beclin‐1‐class III PI3K‐Vps15 core complexes and other proteins. (c) Vesicle elongation and completion mediated by Atg16L complex and LC3. (d) Docking and fusion refer to maturation of autolysosomes promoted by Rab7, LAMP1, LAMP2, SKD1, Vtil 1b and ESCRT complex. (e) In the final stage of degradation and recycling of components, autophagosomal cargoes are digested, and nutrients and inherent energy are recycled.

Figure 2

Core autophagic signalling pathways in cancer cells. Autophagy may decide the ultimate fate of cancer cells for regulation of key survival or death signalling pathways, such as Beclin‐1 complex, PI3K/Akt/mTOR, Ras/Raf/MAPK, BCR‐ABL, p53 and FOXO1 signalling in many types of cancer cells.

Figure 3

Representative natural small molecules targeting autophagic pathways. (a) Curcumin; (b) Resveratrol; (c) Paclitaxe; (d) Oridonin; (e) Quercetin.

Figure 4

Representative natural macromolecules targeting autophagic pathways. (a) Concanavalin A (ConA); (b) Polygonatum cyrtonema lectin (PCL).