Anti-inflammatory effect of Marchantin M contributes to sensitization of prostate cancer cells to docetaxel
Anti-inflammatory effect of Marchantin M contributes to sensitization of prostate cancer cells to docetaxel
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Marchantin M 的抗炎作用有助于前列腺癌细胞对多西他赛的敏感性
DOI：
10.1016/j.canlet.2014.03.019
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发表时间：
2014-06-28
期刊：
影响因子：
9.7
通讯作者：
Lou, Hongxiang
中科院分区：
文献类型：
--
作者：
Niu, Leilei;Deng, Jingti;Lou, Hongxiang
由于促炎细胞因子和趋化因子导致许多类型的人类癌症的恶性，我们研究了双联苯基的抗炎作用，双联苯基是一种天然存在的不同生物活性基团。马钱子素M(Marchantin M，MAR M)是通过对这些化合物的筛选而确定为一种有效的抗炎药，其作用是在不影响细胞增殖的情况下抑制内毒素诱导的HUVEC和PBMCs中IL6、IL1β和CCL2的表达。由于MAR M已被发现具有抗癌活性，我们观察到MAR M处理还导致转移性前列腺癌(PCa)细胞中IL6、IL1β和TNFα的表达减少。这一效应在其他表达高水平促炎细胞因子的癌细胞株中得到了进一步证实。此外，在MAR M处理的PCa细胞中观察到控制许多促炎细胞因子表达的关键转录因子NF-kappa B的失活，其证据是磷酸化P65和随后的磷酸化STAT3的降低。MAR M还抑制胞浆中核因子-kappaB的抑制剂IKBα的磷酸化。然而，当IKBα被敲除时，Mar M减少的磷酸化P65略有增加，这表明Mar M可能靶向IKBα/NF-kappa B信号的上游分子。最后，与IL6阻断相比，MAR M处理的PCa细胞对多西紫杉醇诱导的细胞凋亡的敏感性更高。我们的研究证明了抗炎药MAR M作为佐剂的潜力，以提高传统抗癌药物如多西紫杉醇的疗效。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
As pro-inflammatory cytokines and chemokines contribute to the malignancy of many types of human cancer, we examined the anti-inflammatory effect of bisbibenzyls, a diverse bioactive group of naturally occurring compounds. Marchantin M (Mar M) was identified through a screening process of these compounds as a potent anti-inflammatory agent based on its capacity to inhibit LPS-induced IL6, IL1 beta and CCL2 expression in HUVECs and PBMCs without affecting cell proliferation. Since Mar M has been found to exhibit anticancer activity, we observed that Mar M treatment also resulted in decreases in the expressions of IL6, IL1 beta and TNF alpha in metastatic prostate cancer (PCa) cells. This effect was further confirmed in other cancer cell lines that express high level of pro-inflammatory cytokines. Furthermore, inactivation of NF-kappa B, a critical transcription factor controlling many pro-inflammatory cytokine expressions, was observed in Mar M-treated PCa cells as evidenced by decreased phosphor-p65 and subsequently phosphor-STAT3. Mar M also suppressed phosphorylation of IKB alpha, an inhibitor of NF-kappa B in the cytosol. However, reduced phosphor-p65 by Mar M was slightly increased when knockdown of IKB alpha, suggesting that Mar M may target upstream molecules of IKB alpha/NF-kappa B signaling. Finally, treatment with Mar M resulted in more enhanced-sensitivity of PCa cells to docetaxel-induced apoptosis than that of the IL6 blocking. Our study demonstrates the potential of the anti-inflammatory agent Mar M as an adjuvant to improve the efficacy of traditional anticancer agents such as docetaxel. (C) 2014 Elsevier Ireland Ltd. All rights reserved.