Abstract
Background: Autophagy is a catabolic process through which dysfunctional proteins and organelles are degraded, and that is associated with the proliferation of cancer cells. The aim of this study was to screen approximately 130 kinds of crude drugs used in Japanese Kampo formulas to identify crude drugs that would regulate the proliferation through autophagy of human hepatocellular carcinoma HepG2 cells. Methods: Extracts of each crude drug were prepared using methanol. Protein levels were determined using Western blotting. Cell viability was measured by MTT assay. Results: Among the 130 crude extracts, 24 of them increased LC3-II expression. Among these, Goboshi (burdock fruit), Soboku (sappan wood), Mokko (saussurea root), Rengyo (forsythia fruit), and Hikai (dioscorea) notably suppressed the proliferation of HepG2 cells and increased p62 expression levels, which suggested that these five extracts downregulate the autophagic activity resulting in the accumulation of p62. On the other hand, Hishinomi (water chestnut), Biwayo (loquat leaf), and Binroji (areca) induced cell growth and decreased or were uninvolved with p62 expression levels, which implied that these three extracts might induce autophagy modulators for cell growth. Conclusions: The results suggest that the compounds contained in the crude drugs selected for this study could control cell viability by regulating autophagic activity in HepG2 cells. The isolation and identification of the active compounds in these drugs might lead to the development of agents for autophagy research and cancer chemoprevention.
Highlights
Macroautophagy is an evolutionarily conserved and self-consumption process that degrades cellular organelles and proteins and maintains cellular biosynthesis during nutrient deprivation or metabolic stress [1,2,3,4]
It has been suggested that autophagic activity is intimately related to the proliferation of cancer cells [14,15,16,17,18,19,20,21,22]; we investigated effects the selected
Been suggested that autophagicthe activity is of intimately related to thedrugs proliferation of cancer cells [14,15,16,17,18,19,20,21,22]; we investigated theand effects of the of selected crude drugsextracts on the for of HepG2 cells
Summary
Macroautophagy (hereafter, autophagy) is an evolutionarily conserved and self-consumption process that degrades cellular organelles and proteins and maintains cellular biosynthesis during nutrient deprivation or metabolic stress [1,2,3,4]. The products of degradation are recycled back into the cytosol and are reused to enhance cell survival during nutrient deprivation. Autophagy is a catabolic process through which dysfunctional proteins and organelles are degraded, and that is associated with the proliferation of cancer cells. Results: Among the 130 crude extracts, 24 of them increased LC3-II expression. Goboshi (burdock fruit), Soboku (sappan wood), Mokko (saussurea root), Rengyo (forsythia fruit), and Hikai (dioscorea) notably suppressed the proliferation of HepG2 cells and increased p62 expression levels, which suggested that these five extracts downregulate the autophagic activity resulting in the accumulation of p62. Hishinomi (water chestnut), Biwayo (loquat leaf), and Binroji (areca) induced cell growth and decreased or were uninvolved with p62 expression levels, which implied that these three extracts might induce autophagy modulators for cell growth
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