Podofilox suppresses gastric cancer cell proliferation by regulating cell cycle arrest and the c‑Myc/ATG10 axis

Abstract

Gastric cancer (GC) is a malignancy for which effective therapeutic drugs are limited. Podofilox exhibits antitumor effects in various types of cancer; however, whether it may inhibit GC growth remains unknown. The aim of the present study was to investigate the role of podofilox in GC. Cell Counting Kit-8, colony formation and cell cycle assays were used to detect the role of podofilox on cellular proliferation and the cell cycle, respectively. A microarray was used to detect the transcriptional changes induced by podofilox in GC cells. The results of the present study demonstrated that podofilox inhibited GC cell proliferation and colony formation. The half maximal inhibitory concentration of podofilox in AGS and HGC-27 cells was 2.327 and 1.981 nM, respectively. In addition, treatment with podofilox induced G 0 /G 1 cell cycle arrest. Molecular analysis based on microarray data demonstrated that podofilox altered the expression levels of genes involved in the cell cycle, c-Myc and p53 signaling. Autophagy-related 10 (ATG10), which was highly expressed in GC tissues, was also downregulated by podofilox, as demonstrated by the results of the microarray analysis and immunoblotting. To determine the involvement of ATG10 in GC, ATG10 was knocked down in GC cells by small interfering RNA, which suppressed the proliferation and colony formation of GC cells compared with those observed in the control-transfected cells. Taken together, the results of the present study suggested that podofilox may inhibit GC cell proliferation by preventing the cell cycle progression and regulating the c-Myc/ATG10 signaling pathway.

Natural compounds targeting glycolysis as promising therapeutics for gastric cancer: A review

“…Podofilox at 3.4 nM also inhibited colony formation and reduces the levels of HK2, PKM2, c-Myc, and ATG10. Thus, podofilox inhibits the proliferation of gastric cancer cells by regulating the c-Myc/ATG10 signaling axis ( An et al, 2021 ).…”

Autophagy-related Proteins in Genome Stability: Autophagy-Dependent and Independent Actions

“…In addition to the above-mentioned vital proteins located upstream, other autophagy-related proteins participate in the regulation of the cell cycle. ATG10 is highly expressed in gastric cancer (GC) and may act as an oncogene to regulate the cell cycle and promote abnormal cell proliferation 77 . ATG4 is a kind of cysteine protease that is necessary for the formation of autophagosomes.…”