Autophagy mediates cytotoxicity of human colorectal cancer cells treated with garcinielliptone FC

Shen Jeu Won, Cheng Hsin Yen, Ting Yu Lin, Ya Fen Jiang-Shieh, Chun Nan Lin, Jyun Ti Chen, Chun Li Su

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Abstract

The tautomeric pair of garcinielliptone FC (GFC) is a novel tautomeric pair of polyprenyl benzophenonoid isolated from the pericarps of Garcinia subelliptica Merr. (G. subelliptica, Clusiaceae), a tree with abundant sources of polyphenols. Our previous report demonstrated that GFC induced apoptosis on various types of human cancer cell lines including chemoresistant human colorectal cancer HT-29 cells. In the present study, we observed that many autophagy-related genes in GFC-treated HT-29 cells were up- and down-regulated using a cDNA microarray containing oncogenes and kinase genes. GFC-induced autophagy of HT-29 cells was confirmed by observing the formation of acidic vesicular organelles, LC3 puncta, and double-membrane autophagic vesicles using flow cytometry, confocal microscopy, and transmission electron microscopy, respectively. Inhibition of AKT/mTOR/P70S6K signaling as well as formation of Atg5-Atg12 and PI3K/Beclin-1 complexes were observed using Western blot. Administration of autophagy inhibitor (3-methyladenine and shRNA Atg5) and apoptosis inhibitor Z-VAD showed that the GFC-induced autophagy was cytotoxic form and GFC-induced apoptosis enhanced GFC-induced autophagy. Our data suggest the involvement of autophagy and apoptosis in GFC-induced anticancer mechanisms of human colorectal cancer.

Original languageEnglish
Pages (from-to)497-505
Number of pages9
JournalJournal of Cellular Physiology
Volume233
Issue number1
DOIs
Publication statusPublished - 2018 Jan

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Keywords

  • apoptosis
  • autophagy
  • garcinielliptone FC
  • human colorectal cancer

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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