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 language | English |
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Pages (from-to) | 497-505 |
Number of pages | 9 |
Journal | Journal of Cellular Physiology |
Volume | 233 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2018 Jan |
Keywords
- apoptosis
- autophagy
- garcinielliptone FC
- human colorectal cancer
- Humans
- Autophagy/drug effects
- Gene Expression Regulation, Neoplastic
- Proto-Oncogene Proteins c-akt/metabolism
- Autophagy-Related Protein 5/genetics
- RNA, Messenger/genetics
- Dose-Response Relationship, Drug
- Transfection
- RNA Interference
- Time Factors
- Autophagy-Related Protein 12/genetics
- Triterpenes/pharmacology
- Antineoplastic Agents, Phytogenic/pharmacology
- TOR Serine-Threonine Kinases/metabolism
- Beclin-1/genetics
- Apoptosis/drug effects
- Signal Transduction/drug effects
- Colorectal Neoplasms/drug therapy
- HT29 Cells
- Ribosomal Protein S6 Kinases, 70-kDa/metabolism
- Phosphatidylinositol 3-Kinase/metabolism
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Cell Biology