Green tea polyphenols-induced apoptosis in human osteosarcoma SAOS-2 cells involves a caspase-dependent mechanism with downregulation of nuclear factor-κB
Green tea polyphenols-induced apoptosis in human osteosarcoma SAOS-2 cells involves a caspase-dependent mechanism with downregulation of nuclear factor-κB
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DOI：
10.1016/j.taap.2006.03.013
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发表时间：
2006-10-01
影响因子：
3.8
通讯作者：
Haqqi, Tariq M.
中科院分区：
文献类型：
--
作者：
Bin Hafeez, Bilal;Ahmed, Salahuddin;Haqqi, Tariq M.
骨肉瘤是一种原发性恶性骨肿瘤，其化疗耐药和凋亡逃避的发生往往与组成性核因子-κ B（NF-κ B）的激活有关。在这里，我们研究了绿色茶（GTP），已被证明对各种恶性细胞系具有抗肿瘤作用的多酚馏分抑制人骨肉瘤SAOS-2细胞的生长和诱导凋亡的能力。用GTP（20-60 μ g/ml）处理SAOS-2细胞导致细胞增殖减少和诱导凋亡，这与NF-κ B/p65的核DNA结合减少以及细胞质和细胞核中NF-κ B/p65和p50水平降低相关。GTP处理细胞减少I κ B-α磷酸化，但对其蛋白表达没有影响。此外，GTP处理导致IKK-α和IKK-β的抑制，IKK-α和IKK-β是磷酸化I κ B-α的上游激酶。SAOS-2细胞凋亡率的增加伴随着Bcl-2蛋白表达的减少和Bax蛋白表达的增加。GTP处理SAOS-2细胞还导致半胱天冬酶的显著活化，这通过这些细胞中裂解的半胱天冬酶-3和半胱天冬酶-8的水平增加而明显。Caspase-3特异性抑制剂Ac-Asp-Glu-Val-Asp-CHO（Ac-DEVD-CHO）和Caspase-3通用抑制剂N-苄氧羰基-Val-Ala-Asp（OMe）-氟甲基酮（Z-VAD-FMK）处理SAOS-2细胞可使SAOS-2细胞免于GTP诱导的凋亡。综上所述，这些结果表明GTP是骨肉瘤的候选治疗剂，其通过激活半胱天冬酶和抑制NF-κ B介导其抗增殖和凋亡作用。(c)2006年爱思唯尔公司All rights reserved.
Development of chemotherapy resistance and evasion from apoptosis in osteosarcoma, a primary malignant bone tumor, is often correlated with constitutive nuclear factor-kappa B (NF-kappa B) activation. Here, we investigated the ability of a polyphenolic fraction of green tea (GTP) that has been shown to have antitumor effects on various malignant cell lines to inhibit growth and induce apoptosis in human osteosarcoma SAOS-2 cells. Treatment of SAOS-2 cells with GTP (20-60 mu g/ml) resulted in reduced cell proliferation and induction of apoptosis, which correlated with decreased nuclear DNA binding of NF-kappa B/p65 and lowering of NF-kappa B/p65 and p50 levels in the cytoplasm and nucleus. GTP treatment of cells reduced I kappa B-alpha phosphorylation but had no effect on its protein expression. Furthermore, GTP treatment resulted in the inhibition of IKK-alpha and IKK-beta, the upstream kinases that phosphorylate I kappa B-alpha. The increase in apoptosis in SAOS-2 cells was accompanied with decrease in the protein expression of Bcl-2 and concomitant increase in the levels of Bax. GTP treatment of SAOS-2 cells also resulted in significant activation of caspases as was evident by increased levels of cleaved caspase-3 and caspase-8 in these cells. Treatment of SAOS-2 cells with a specific caspase-3 inhibitor Ac-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO) and general caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone (Z-VAD-FMK) rescued SAOS-2 cells from GTP-induced apoptosis. Taken together, these results indicate that GTP is a candidate therapeutic for osteosarcoma that mediates its antiproliferative and apoptotic effects via activation of caspases and inhibition of NF-kappa B. (c) 2006 Elsevier Inc. All rights reserved.