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.
| Language | English |
|---|---|
| Pages | 497-505 |
| Number of pages | 9 |
| Journal | Journal of Cellular Physiology |
| Volume | 233 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2018 Jan 1 |
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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 journal › Article
}
TY - JOUR
T1 - Autophagy mediates cytotoxicity of human colorectal cancer cells treated with garcinielliptone FC
AU - Won, Shen Jeu
AU - Yen, Cheng Hsin
AU - Lin, Ting Yu
AU - Jiang-Shieh, Ya Fen
AU - Lin, Chun Nan
AU - Chen, Jyun Ti
AU - Su, Chun Li
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - apoptosis
KW - autophagy
KW - garcinielliptone FC
KW - human colorectal cancer
UR - http://www.scopus.com/inward/record.url?scp=85018319744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018319744&partnerID=8YFLogxK
U2 - 10.1002/jcp.25910
DO - 10.1002/jcp.25910
M3 - Article
VL - 233
SP - 497
EP - 505
JO - Journal of Cellular Physiology
T2 - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
IS - 1
ER -