Inhibition of autophagy enhances DENSpm-induced apoptosis in human colon cancer cells in a p53 independent manner

Cellular Oncology (Dordrecht)
Ajda Coker GürkanNarcin Palavan Unsal

Abstract

One of the recently developed polyamine (PA) analogues, N 1 ,N11-diethylnorspermine (DENSpm), has been found to act as an apoptotic inducer in melanoma, breast, prostate and colon cancer cells. Also, its potential to induce autophagy has been established. Unfolded protein responses and starvation of amino acids are known to trigger autophagy. As yet, however, the molecular mechanism underlying PA deficiency-induced autophagy is not fully clarified. Here, we aimed to determine the apoptotic effect of DENSpm after autophagy inhibition by 3-methyladenine (3-MA) or siRNA-mediated Beclin-1 silencing in colon cancer cells. The apoptotic effects of DENSpm after 3-MA treatment or Beclin-1 silencing were determined by PI and AnnexinV/PI staining in conjunction with flow cytometry. Intracellular PA levels were measured by HPLC, whereas autophagy and the expression profiles of PA key players were determined in HCT116, SW480 and HT29 colon cancer cells by Western blotting. We found that DENSpm-induced autophagy was inhibited by 3-MA treatment and Beclin-1 silencing, and that apoptotic cell death was increased by PA depletion and spermidine/spermine N1-acetyltransferase (SSAT) upregulation. We also found that autophagy inhibition led to DEN...Continue Reading

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Citations

Jan 16, 2019·Cellular Oncology (Dordrecht)·Safieh Ebrahimi, Seyed Isaac Hashemy
Apr 12, 2019·Medicinal Research Reviews·Xin SunJianbin Zhang
Jul 28, 2020·Carcinogenesis·Takahiro HamoyaMichihiro Mutoh
Oct 12, 2018·Medicinal Research Reviews·Hendrik FolkertsValerie R Wiersma

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Methods Mentioned

BETA
fluorescence microscopy
transfection
scraping
protein assay
light microscopy
flow cytometry
FACS
flow

Software Mentioned

GraphPad
C6
GraphPad Prism
Image J

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