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KMID : 1161420120150020152
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Journal of Medicinal Food
2012 Volume.15 No. 2 p.152 ~ p.160
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Antiproliferative Effects of Dangyuja (Citrus grandis Osbeck) Leaves Through Suppression of Constitutive Signal Transducer and Activator of Transcription 3 Activation in Human Prostate Carcinoma DU145 Cells
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Chiang Shu Yuan
Kim Sung-Moo
Kim Chul-Won
Um Jae-Young
Park Kyung-Ran
Kim Seong-Won
Lee Seok-Geun
Jang Hyeung-Jin
Nam Dong-Woo
Ahn Kyoo-Seok
Kim Sung-Hoon
Choi Seung-Hoon
Shim Bum-Sang
Na Yun-Cheol
Jeong Eun-Kyung
Cho So-Mi K.
Ahn Kwang-Seok
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Abstract
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Although Dangyuja (Citrus grandis Osbeck) exhibits anti-inflammatory and anticancer activities, its molecular targets and pathways, especially in human prostate cancer cells, are not fully understood. In this study, the antiproliferative effect of Dangyuja leaves through the signal transducer and activator of transcription (STAT) 3 signaling pathway was investigated in human prostate carcinoma DU145 cells. The solvent fractions (n-hexane, chloroform, ethyl acetate, and n-butanol) were obtained from a crude extract (80% methanol extract) of Dangyuja leaves. We first found that the chloroform fraction of Dangyuja leaves (DCF) was the most cytotoxic against DU145 cells. DCF inhibited constitutive STAT3 activation through blocking upstream Janus-like kinase 2 and c-Src. Consistent with STAT3 inactivation, DCF down-regulated the expression of STAT3 target genes, including bcl-2, bcl-xl, and cyclin D1; this correlated with the suppression of proliferation, the accumulation of cell cycle at the sub-G1 phase, and the induction of apoptosis. Furthermore, DCF exerted a relatively minor effect on the growth of human prostate noncancerous RWPE-1 cells. Nobiletin, a major active constituent of DCF, could induce apoptosis via the suppression of constitutive STAT3 activation. Overall, our results indicate that the anti-inflammatory and anticancer activities previously assigned to DCF may be mediated partially through the suppression of the STAT3 signaling.
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KEYWORD
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apoptosis, Citrus grandis Osbeck, Dangyuja, prostate cancer, signal transducer and activation of transcription 3
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