title: anti-tumor effect of AlkB homolog 3 knockdown in hormone- independent prostate cancer cells.
abstract: Castrate resistant prostate cancer (CRPC) is a disease that is resistant to both hormone therapy and chemotherapy. At present, no curative therapy for CRPC has been established. Therefore, it is necessary to determine a novel molecular target for the development of therapeutic agents. We previously reported that AlkB homolog 3 (ALKBH3) is highly expressed in prostate cancer but not in benign prostatic hyperplasia or in normal prostate epithelium and that the expression levels of ALKBH3 protein are significantly correlated with the hormone-independent state of prostate cancer. Moreover, ALKBH3 regulates the invasion of prostate cancer cells via the regulation of matrix metalloproteinase 9. Here, we show that ALKBH3 gene silencing markedly induces apoptosis in hormone-independent prostate cancer cell line DU145 but not in the normal prostate epithelial cell line PNT2. Moreover, the in vivo tumorigenicity of DU145 cells was significantly inhibited by the administration of ALKBH3 siRNA. Furthermore, the anchorage-independent growth of DU145 cells was inhibited by ALKBH3 knockdown and promoted by ALKBH3 overexpression, significantly. ALKBH3 shRNA-expressing prostate cancer cells formed significantly smaller tumors than those of control shRNA transfectants in an in vivo xenograft model. These findings suggest that ALKBH3 is a promising target molecule for the development of CRPC therapeutic agents.
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: Y
authors.initials: Y
authors.lastname: Ueda
authors.forename: H
authors.initials: H
authors.lastname: Hase
authors.forename: K
authors.initials: K
authors.lastname: Kitae
authors.forename: Y
authors.initials: Y
authors.lastname: Fusamae
authors.forename: S
authors.initials: S
authors.lastname: Masai
authors.forename: T
authors.initials: T
authors.lastname: Inagaki
authors.forename: Y
authors.initials: Y
authors.lastname: Saigo
authors.forename: S
authors.initials: S
authors.lastname: Hirasawa
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: I
authors.initials: I
authors.lastname: Ohshio
authors.forename: Y
authors.initials: Y
authors.lastname: Makino
authors.forename: N
authors.initials: N
authors.lastname: Konishi
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Tsujikawa
mesh_terms: D000071500:AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D045643:DNA Repair Enzymes / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D049308:Dioxygenases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D049308:Dioxygenases; C486439:ALKBH3 protein, human; D000071500:AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase; D045643:DNA Repair Enzymes