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

Research output: Contribution to journalArticle

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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.

LanguageEnglish
Pages497-505
Number of pages9
JournalJournal of Cellular Physiology
Volume233
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

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Autophagy
Cytotoxicity
Colorectal Neoplasms
Cells
HT29 Cells
Apoptosis
Clusiaceae
Genes
Garcinia
70-kDa Ribosomal Protein S6 Kinases
Flow cytometry
garcinielliptone FC
Confocal microscopy
Polyphenols
Microarrays
Oligonucleotide Array Sequence Analysis
Transmission Electron Microscopy
Phosphatidylinositol 3-Kinases
Oncogenes
Confocal Microscopy

Keywords

  • apoptosis
  • autophagy
  • garcinielliptone FC
  • human colorectal cancer

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Autophagy mediates cytotoxicity of human colorectal cancer cells treated with garcinielliptone FC. / Won, Shen Jeu; Yen, Cheng Hsin; Lin, Ting Yu; Jiang-Shieh, Ya Fen; Lin, Chun Nan; Chen, Jyun Ti; Su, Chun Li.

In: Journal of Cellular Physiology, Vol. 233, No. 1, 01.01.2018, p. 497-505.

Research output: Contribution to journalArticle

Won, Shen Jeu ; Yen, Cheng Hsin ; Lin, Ting Yu ; Jiang-Shieh, Ya Fen ; Lin, Chun Nan ; Chen, Jyun Ti ; Su, Chun Li. / Autophagy mediates cytotoxicity of human colorectal cancer cells treated with garcinielliptone FC. In: Journal of Cellular Physiology. 2018 ; Vol. 233, No. 1. pp. 497-505.
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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.",
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