title: Gleditsia sinensis Thorn Attenuates the Collagen-Based Migration of PC3 Prostate Cancer Cells through the Suppression of α2β1 Integrin Expression.
abstract: Gleditsia sinensis thorns (GST) have been used as a traditional medicine for carbuncles and skin diseases. The purpose of this study was to decide whether non-toxicological levels of water extract of GST (WEGST) are effective in inhibiting the progress of prostate cancer formation and to identify the target molecule involved in the WEGST-mediated inhibitory process of prostate cancer cell migration and in vivo tumor formation. Through the Boyden chamber migration assay, we found that non-toxic levels of WEGST could not attenuate the PC3 migration to the bottom area coated with serum but significantly inhibited PC3 cell migration to the collagen-coated bottom area. We also found that non-toxic levels of WEGST significantly attenuated collagen against adhesion. Interestingly, ectopic administration of WEGST could not affect the expression of α2β1 integrin, which is known as a receptor of collagen. However, when the PC3 cells adhered to a collagen-coated plate, the expression of α2 integrin but not that of β1 integrin was significantly inhibited by the administration of non-toxic levels of WEGST, leading to the inhibition of focal adhesion kinase (FAK) phosphorylation. Furthermore, oral administration of WEGST (25 mg/kg/day) significantly inhibited the size of a PC3 cell-xenografted tumor. Taken together, these results suggest a novel molecular mechanism for WEGST to inhibit prostate cancer progression at particular stages, such as collagen-mediated adhesion and migration, and it might provide further development for the therapeutic use of WEGST in the treatment of prostate cancer progression.
authors.affiliation: Department of Nano-Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 406-772, Korea. lovedbtnwls@naver.com.
authors.forename: Sujin
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Seoul 440-746, Korea. pkm1001@skku.edu.
authors.forename: Ki Moon
authors.initials: KM
authors.lastname: Park
authors.affiliation: Department of Nano-Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 406-772, Korea. seungho@inu.ac.kr.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D031501:Gleditsia / Q000737:chemistry*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D038982:Integrin alpha2beta1; D010936:Plant Extracts; D003094:Collagen; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: Gleditsia sinensis; collagen; migration; prostate cancer; α2β1 integrin