MAP30 inhibits autophagy through enhancing acetyltransferase p300 and induces apoptosis in acute myeloid leukemia cells

Oncol Rep. 2016 Jun;35(6):3705-13. doi: 10.3892/or.2016.4705. Epub 2016 Mar 24.

Abstract

Momordica anti-human immunodeficiency virus protein of 30 kDa (MAP30) has been shown to exhibit potent antitumor activities against several solid tumors. In the present investigation we demonstrated that MAP30 significantly inhibited the proliferation of acute myeloid leukemia (AML) HL-60 and THP-1 cell lines and patient AML cells through autophagy inhibition and apoptosis induction. Intriguingly, MAP30-induced cell death and apoptosis were partially rescued in combination with an autophagy activator rapamycin, and aggravated in combination with an autophagy inhibitor bafilomycin A1 in HL-60 cells, suggesting that autophagy is a pro-survival signal and its inhibition contributes to the induction of apoptosis in MAP30‑induced cell death. Further mechanism analysis demonstrated that MAP30 enhanced p300, and C646, a selective inhibitor of p300, markedly promoted autophagy and partially rescued the MAP30-induced cell death in HL-60 cells and patient AML cells. Collectively, our findings suggest that apoptosis and autophagy act cooperatively to elicit MAP30-induced cell death and MAP30 may be a potential antitumor drug candidate against AML.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Benzoates / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • HL-60 Cells
  • Humans
  • Leukemia, Myeloid, Acute / pathology*
  • Macrolides / pharmacology
  • Momordica charantia / metabolism
  • Nitrobenzenes
  • Plant Extracts / pharmacology
  • Pyrazoles / pharmacology
  • Pyrazolones
  • Ribosome Inactivating Proteins, Type 2 / pharmacology*
  • Sirolimus / pharmacology
  • p300-CBP Transcription Factors / antagonists & inhibitors

Substances

  • 4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid
  • Antineoplastic Agents, Phytogenic
  • Benzoates
  • MAP30 protein, Momordica charantia
  • Macrolides
  • Nitrobenzenes
  • Plant Extracts
  • Pyrazoles
  • Pyrazolones
  • Ribosome Inactivating Proteins, Type 2
  • bafilomycin A1
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Sirolimus