Korean J Anat.  2009 Jun;42(2):83-92.

Apoptotic Effect of Co-treatment with Chios Gum Mastic and HS-1200 on G361 Human Melanoma Cell Line

• Hur YJ
• Kim YK
• Kwak HH
• Kim GC
• Lee SE
• Kim IR
• Kim CH
• Park BS

Abstract

Chios gum mastic (CGM) is a resinous exudate obtained from the stem and the main leaves of Pistacia lenticulus tree native to Mediterranean areas. Recently it reported that CGM induce apoptosis in a few cancer cells in vitro. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of cotreatment with a natural product, CGM and a CDCA derivative, HS-1200 on G361 human melanoma cells. To investigate whether the co-treatment of CGM and HS-1200 compared with each single treatment efficiently reduced the viability of G361 cells, MTT assay was conducted. To investigate augmentation of apoptosis in G631 cells co-treated with CGM and HS-1200, DNA electrophoresis, Hoechst staining, proteasome activity assay, flow cytometry, Westen blot analyses, immunofluorescent staining and confocal microscopy were performed. In this study, G361 cells co-treated with CGM and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, DNA fragmentation, the reduction of MMP and proteasome activity, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF and DFF40 (CAD) onto nuclei, activation of caspase-9, caspase-3, PARP and DFF45 (ICAD), and up-regulation of Bax whereas each single treated G361 cells did not. Although the single treatment of 40 micro/mL CGM or 25 micro HS-1200 for 24 hrs did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore, combination therapy of CGM and HS-1200 could be considered, in the future, as an alternative therapeutic strategy for human melanoma.

Keyword

Chios gum mastic (CGM); Synthetic bile acid; HS-1200; Apoptosis; Human melanoma cells (G361 cells)

MeSH Terms

Apoptosis
Bile Acids and Salts
Caspase 3
Caspase 9
Cell Line
Chenodeoxycholic Acid
Cytochromes c
Cytosol
DNA
DNA Fragmentation
Electrophoresis
Exudates and Transudates
Flow Cytometry
Gingiva
Humans
Melanoma
Microscopy, Confocal
Pistacia
Proteasome Endopeptidase Complex
Resins, Plant
Trees
Up-Regulation
Bile Acids and Salts
Caspase 3
Caspase 9
Chenodeoxycholic Acid
Cytochromes c
DNA
Proteasome Endopeptidase Complex
Resins, Plant