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KMID : 0355820170380010013
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Korean Journal of Oral Anatomy
2017 Volume.38 No. 1 p.13 ~ p.30
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Mechanism underlying Chios gum mastic-induced cell cycle arrest and apoptosis of the G361 human melanoma cell line
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Kim In-Ryoung
Kang Hae-Mi
Yu Su-Bin
Park Bong-Soo
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Abstract
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Chios gum mastic (CGM) is a resin extracted from the stem and leaves of Pistacia lentiscus L. var. chia. It has been used as a traditional medicine in many Mediterranean countries. Recently, numerous researches have demonstrated that CGM induces cell cycle arrest and apoptosis in many cancer cells. In the present study, an alter?ation of the cell cycle and induction of apoptosis by CGM treatment on malignant melanoma was investigated. CGM treatment showed the inhibition of cell viability in a dose- and time-dependent manner on the G631 melanoma cell line. Apoptotic hallmarks, such as nuclear condensation and DNA fragmentation, were also identified in CGM-treated cells. Several lines of apoptotic manifestation were demonstrated. The proapoptotic factor Bax was increased in a time-dependent manner, leading to MMP loss, proteasome activity reduction, AIF translocation, and cytochrome c release. Activation of caspases, such as caspase-9, -7, and -3, led to the cleav?age of PARP and DFF45 (ICAD). DFF40 (CAD) was translocated into the nucleus from the cytoplasm of the CGM-treated G361 cells. CGM halted the cell cycle progression by G1 arrest and the reduction in the level of cyclin-dependent kinases (CDKs). Accumulation of p53 protein was not observed in cells treated with CGM for 24-72 h. The level of p27KIPI was increased by CGM treatment only for an initial 24-h period. Cyclin Dl, D3, and E protein levels were diminished in CGM-treated cells. Therefore, it is possible that CGM treatment could serve as a novel therapeutic strategy against human melanoma.
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KEYWORD
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Chios gum mastic, Cell cycle arrest, Apoptosis, Melanoma
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