Abstract
Autophagy is an evolutionarily conserved pathway to degrade damaged proteins and organelles for subsequent recycling in cells during times of nutrient deprivation. This process plays an important role in tumor development and progression, allowing cancer cells to survive in nutrient-poor environments. The plant kingdom provides a powerful source for new drug development to treat cancer. Several plant extracts induce autophagy in cancer cells. However, little is known about the role of plant extracts in autophagy inhibition, particularly autophagy-related (ATG) proteins. In this study, we employed S-tagged gamma-aminobutyric acid receptor associated protein like 2 (GABARAPL2) as a reporter to screen 48 plant extracts for their effects on the activity of autophagy protease ATG4B. Xanthium strumarium and Tribulus terrestris fruit extracts were validated as potential ATG4B inhibitors by another reporter substrate MAP1LC3B-PLA2. The inhibitory effects of the extracts on cellular ATG4B and autophagic flux were further confirmed. Moreover, the plant extracts significantly reduced colorectal cancer cell viability and sensitized cancer cells to starvation conditions. The fruit extract of X. strumarium consistently diminished cancer cell migration and invasion. Taken together, the results showed that the fruit of X. strumarium may have an active ingredient to inhibit ATG4B and suppress the proliferation and metastatic characteristics of colorectal cancer cells.
Highlights
IntroductionAutophagy is a self-eating pathway in eukaryotic cells that recycles proteins and organelles to generate substrates for new synthesis in cells during times of nutrient deprivation or stresses
Autophagy is a self-eating pathway in eukaryotic cells that recycles proteins and organelles to generate substrates for new synthesis in cells during times of nutrient deprivation or stresses.This evolutionarily conserved pathway is highly associated with many diseases, cancer progression [1]
Because our present results showed that the fruit extracts from X. strumarium and T. terrestris can block autophagic flux, these results suggest the extracts might inhibit tumor progression in certain types of cancer or conditions
Summary
Autophagy is a self-eating pathway in eukaryotic cells that recycles proteins and organelles to generate substrates for new synthesis in cells during times of nutrient deprivation or stresses. This evolutionarily conserved pathway is highly associated with many diseases, cancer progression [1]. It has been validated to have antitumor effects in a certain subset of cancer patients, such as those with glioma and colorectal cancer [6]. These results indicate that the autophagy inhibitor may improve cancer therapy in certain types of cancer
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