title: Geranylgeranylacetone induces apoptosis via the intrinsic pathway in human melanoma cells.
abstract: The aim of this study was to test the anti-cancer effects of geranylgeranylacetone (GGA), an isoprenoid compound, on human melanoma cells. Human melanoma cell lines G361, SK-MEL-2, and SK-MEL-5 were treated with GGA at various doses (1-100μM). Cell viability was measured by crystal violet assay. Western blot analysis was adopted to detect marker proteins of apoptosis. GGA significantly reduced the viability of G361, SK-MEL-2, and SK-MEL-5 human melanoma cells at concentrations above 10μM. Western blot analysis showed the phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) after GGA treatment, as well as activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP) cleavage. GGA also induced p53 and Bax expression, but did not affect expression of Bcl-2 and MITF. These findings suggest that GGA induces apoptosis through the intrinsic pathway. Accordingly, GGA should be considered for further development as a potential agent for melanoma.
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 84 Heukseok-ro Dongjak-gu, Seoul 06974, Republic of Korea.
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Jo
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 84 Heukseok-ro Dongjak-gu, Seoul 06974, Republic of Korea.
authors.forename: Hyo-Soon
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Thomas J. Long School of Pharmacy, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA.
authors.forename: Myo-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 84 Heukseok-ro Dongjak-gu, Seoul 06974, Republic of Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Yun
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 84 Heukseok-ro Dongjak-gu, Seoul 06974, Republic of Korea.
authors.forename: Kwang Jin
authors.initials: KJ
authors.lastname: Baek
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 84 Heukseok-ro Dongjak-gu, Seoul 06974, Republic of Korea.
authors.forename: Nyoun Soo
authors.initials: NS
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 84 Heukseok-ro Dongjak-gu, Seoul 06974, Republic of Korea. Electronic address: ds_kim@cau.ac.kr.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004224:Diterpenes; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C031049:geranylgeranylacetone
keywords: Apoptosis; Caspase; Geranylgeranylacetone; Melanoma; Skin cancer