title: Hexane extract of aged black garlic reduces cell proliferation and attenuates the expression of ICAM-1 and VCAM‑1 in TNF-α-activated human endometrial stromal cells.
abstract: Increasing evidence indicates the potentially crucial roles of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the pathological process underlying endometriosis. The present study aimed to investigate the effects of a hexane extract of aged black garlic (HEABG) on the proliferation and expression of ICAM-1 and VCAM-1 in tumor necrosis factor-α (TNF-α)-activated human endometrial stromal cells (HESCs) isolated from patients with endometriosis. HESCs were isolated from endometriotic tissues obtained from women with advanced endometriosis who underwent laparoscopic surgery for ovarian endometrioma (n=18). Cell proliferation and cell cycle analysis were assessed by WST-1 assay and flow cytometry, respectively. The expression of ICAM-1 and VCAM-1 was measured by flow cytometry, immunofluorescence staining, immunoblotting and quantitative reverse transcriptase-PCR. The secretion of interleukin-6 (IL-6) was determined by enzyme-linked immunosorbent assay (ELISA). The activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) was detected by electrophoretic mobility shift assay (EMSA) and the activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 MAPK was analyzed by immunoblotting. Cell proliferation and cell cycle progression were significantly suppressed by HEABG in the TNF-α-induced HESCs through the inhibition of the ERK and JNK signaling pathways. Remarkably, the treatment of the HESCs with HEABG potently suppressed the TNF-α-induced ICAM-1 and VCAM-1 transcript and protein expression by inhibiting the activation of NF-κB and AP-1 transcription factors. Our results suggest that HEABG may be effective in the prevention and treatment of endometriosis in humans.
authors.affiliation: Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan 602-739, Republic of Korea.
authors.forename: Ki-Hyung
authors.initials: KH
authors.lastname: Kim
authors.forename: Jin Kyeong
authors.initials: JK
authors.lastname: Park
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Choi
authors.forename: Youn-Han
authors.initials: YH
authors.lastname: Kim
authors.forename: Eun Na
authors.initials: EN
authors.lastname: Lee
authors.forename: Ja-Rang
authors.initials: JR
authors.lastname: Lee
authors.forename: Heui-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Sun-Yong
authors.initials: SY
authors.lastname: Baek
authors.forename: Bong-Seon
authors.initials: BS
authors.lastname: Kim
authors.forename: Kyu-Sup
authors.initials: KS
authors.lastname: Lee
authors.forename: Sik
authors.initials: S
authors.lastname: Yoon
mesh_terms: D000328:Adult; D002453:Cell Cycle / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005737:Garlic / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D021381:Protein Transport / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1