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

• Published in: Journal of cellular physiology 2018-01, Vol.233 (1), p.497-505
• Main Authors: Won, Shen‐Jeu, Yen, Cheng‐Hsin, Lin, Ting‐Yu, Jiang‐Shieh, Ya‐Fen, Lin, Chun‐Nan, Chen, Jyun‐Ti, Su, Chun‐Li
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Autophagy-Related Protein 12 - genetics; Autophagy-Related Protein 12 - metabolism; Autophagy-Related Protein 5 - genetics; Autophagy-Related Protein 5 - metabolism; Beclin-1 - genetics; Beclin-1 - metabolism; Cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - ultrastructure; Confocal microscopy; Cytometry; Cytotoxicity; DNA microarrays; Dose-Response Relationship, Drug; Electron microscopy; Flow cytometry; garcinielliptone FC; Gene Expression Regulation, Neoplastic; Genes; HT29 Cells; human colorectal cancer; Humans; Inhibitors; Membrane vesicles; Organelles; Phagocytosis; Phosphatidylinositol 3-Kinase - metabolism; Polyphenols; Proto-Oncogene Proteins c-akt - metabolism; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; RNA Interference; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; Time Factors; TOR protein; TOR Serine-Threonine Kinases - metabolism; Toxicity; Transfection; Transmission electron microscopy; Triterpenes - pharmacology; Tumor cell lines
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.25910

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. 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. GFC‐induced autophagy was cytotoxic form and GFC‐induced apoptosis enhanced GFC‐induced autophagy.