title: Pigment epithelium-derived factor inhibits lysosomal degradation of Bcl-xL and apoptosis in HepG2 cells.
abstract: Pigment epithelium-derived factor (PEDF) has several biological actions on tumor cells, but its effects are cell-type dependent. The aim of this study was to examine the pathophysiological role of PEDF in hepatocellular carcinoma (HCC). PEDF expression was examined in various hepatoma cell lines and human HCC tissues, and was seen in various hepatoma cell lines including HepG2 cells. In human HCC tissues, PEDF expression was higher than in adjacent non-HCC tissues. In addition, serum PEDF levels were higher in HCC patients than in non-HCC patients, and curative treatment of HCC caused significant reductions in serum PEDF levels compared with pretreatment levels. In vitro experiments, camptothecin (CPT) was used to induce apoptosis and the effect of PEDF was investigated by knockdown of the PEDF gene in CPT-treated HepG2 cells. Knockdown of the PEDF gene enhanced CPT-induced apoptosis, simultaneously down-regulating Bcl-xL expression in HepG2 cells. Expression of apoptosis-related molecules and effects of bafilomycin A1 on CPT-induced apoptosis were also examined in PEDF gene knockdown HepG2 cells. Treatment with bafilomycin A1 suppressed CPT-induced decreases in Bcl-xL expression and increases in apoptosis in PEDF gene knockdown HepG2 cells. PEDF may, therefore, exert anti-apoptotic effects through inhibition of lysosomal degradation of Bcl-xL in CPT-treated HepG2 cells.
authors: Department of Digestive Disease Information and Research, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. takumi@med.kurume-u.ac.jp
authors: Takumi
authors: T
authors: Kawaguchi
authors: Sho-Ichi
authors: S
authors: Yamagishi
authors: Minoru
authors: M
authors: Itou
authors: Koji
authors: K
authors: Okuda
authors: Shuji
authors: S
authors: Sumie
authors: Ryoko
authors: R
authors: Kuromatsu
authors: Masahiro
authors: M
authors: Sakata
authors: Mitsuhiko
authors: M
authors: Abe
authors: Eitaro
authors: E
authors: Taniguchi
authors: Hironori
authors: H
authors: Koga
authors: Masaru
authors: M
authors: Harada
authors: Takato
authors: T
authors: Ueno
authors: Michio
authors: M
authors: Sata
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism; D003720:Densitometry; D005136:Eye Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D018942:Macrolides / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015843:Serpins / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D002166:Camptothecin; D021983:Cyclophilins; D005136:Eye Proteins; D007976:Leupeptins; D018942:Macrolides; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015843:Serpins; D051020:bcl-X Protein; D000099174:Pigment Epithelium-Derived Factor; C040929:bafilomycin A1; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde