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
Y1 - 2018/1
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
KW - Humans
KW - Autophagy/drug effects
KW - Gene Expression Regulation, Neoplastic
KW - Proto-Oncogene Proteins c-akt/metabolism
KW - Autophagy-Related Protein 5/genetics
KW - RNA, Messenger/genetics
KW - Dose-Response Relationship, Drug
KW - Transfection
KW - RNA Interference
KW - Time Factors
KW - Autophagy-Related Protein 12/genetics
KW - Triterpenes/pharmacology
KW - Antineoplastic Agents, Phytogenic/pharmacology
KW - TOR Serine-Threonine Kinases/metabolism
KW - Beclin-1/genetics
KW - Apoptosis/drug effects
KW - Signal Transduction/drug effects
KW - Colorectal Neoplasms/drug therapy
KW - HT29 Cells
KW - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
KW - Phosphatidylinositol 3-Kinase/metabolism
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
C2 - 28294332
AN - SCOPUS:85018319744
VL - 233
SP - 497
EP - 505
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
IS - 1
ER -