Apoptotic Effect of Co-Treatment with a Natural Product, Chios Gum Mastic, and a Proteasome Inhibitor, Lactacystin, on Human Osteosarcoma Cells

• 발행기관: 대한해부학회
• 저자명: Chul-Jung Baek Ji-Ye Heo Gyoo-Cheon Kim Hyun-Ho Kwak In-Ryoung Kim Seung-Eun Lee Chul-Hoon Kim Na-Young Jeong Bong-Soo Park
• 간행물 정보: 『대한해부학회지』제41권 제2호, 129~138쪽, 전체 10쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2008.04.30

영문 초록

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 was reported that CGM induced apoptosis in a few cancer cells in vitro. Since recent studies indicated the synergistic interactions between the apoptotic stimulus and a proteasome inhibitor, the ubiquintin-proteasome pathway has become an attractive target in cancer therapy. And to date, there has been no report of the synergistic apoptotic effect between CGM and a proteasome inhibitor to become an attractive target in cancer therapy. Therefore, this study was undertaken to investigate the synergistic apoptotic effect of co-treatment with a natural product, CGM, and a proteasome inhibitor, lactacystin, on human osteosarcoma (HOS) cells. To investigate whether the co-treatment of CGM and lactacystin compared with each single treatment efficiently induced apoptosis on HOS cells, MTT assay, DNA electrophoresis, Hoechst staining, DNA hypoploidy assay, Westen blot analysis, immunofluorescent staining, proteasome activity and mitochondrial membrane potential (MMP) change were performed. In this study, HOS cells co-treated with CGM and lactacystin showed several lines of apoptotic manifestation such as nuclear condensation, 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, and activation of caspase-7, caspase-3, PARP and DFF45 (ICAD) whereas each single treated HOS cells hardly showed. We presented data indicating that the co-treatment of CGM and lactacystin induced potentially apoptosis whereas each single treatment did slightly. Moreover, the co-treatment of CGM and lactacystin potentiated the inhibition of proteasome activity. Therefore, our data provide the possibility that combination therapy of CGM and lactacystin could be considered as a novel therapeutic strategy for human osteosarcoma.

키워드

Chios gum mastic Lactacystin Apoptosis Human osteosarcoma cells