College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA
Anticancer Res. 2014 Jun;34(6):2763-70.
Monocyte chemotactic protein-1 (MCP-1/CCL2) is released by tumor tissues, serving as a potent chemokine enabling directional homing of mononuclear cells to tumor tissue, which subsequently differentiate into tumor-associated macrophages (TAMs) via TGFβ1 signaling. TAMs readily invade tumor tissue and continue to synthesize pro-oncogenic proteins including tumor growth factors, matrix proteases (metastasis), angiogenic factors (neovascularization) and CCL2. Substances, which can attenuate or block the initial release of CCL2 have been shown to prevent cancer-associated inflammative pro-oncogenic processes. In the current study, we investigated the effects of the organosulfur compound diallyl disulfide (DADS), a natural constituent of Allium sativum (garlic) on suppression of TNFα-induced release of CCL2 from triple-negative human breast tumor (MDA-MB-231) cells. Using an initial adipokine/chemokine protein panel microarray, the data show a predominant expression profile in resting/untreated MDA-MB-231 cells for sustained release of IL6, IL8, plasminogen Activator Inhibitor 1 and TIMP1/2. Treatment with TNFα (40 ng/ml) had no effect on many of these molecules, with a single major elevation in release of CCL2 (~1,300-fold up-regulation). TNFα-induced CCL2 release was reversed by a sub-lethal concentration of DADS (100 μM), evident in antibody based assays. These findings provide evidence to support another avenue of anticancer/chemopreventative properties attributable to garlic constituents through immunomodulation.
单核细胞趋化蛋白-1（MCP-1/CCL2）由肿瘤组织释放，作为一种有效的趋化因子，能够使单核细胞定向归巢至肿瘤组织，随后通过 TGFβ1 信号转导分化为肿瘤相关巨噬细胞（TAMs）。TAMs 容易浸润肿瘤组织，并继续合成促癌蛋白，包括肿瘤生长因子、基质蛋白酶（转移）、血管生成因子（新生血管形成）和 CCL2。已经证明，能够减弱或阻断 CCL2 初始释放的物质可以防止与癌症相关的炎症性促癌过程。在本研究中，我们研究了有机硫化合物二烯丙基二硫化物（DADS）对抑制 TNFα 诱导的三阴性人乳腺癌（MDA-MB-231）细胞释放 CCL2 的影响。使用初始的脂肪因子/趋化因子蛋白谱微阵列，数据显示静止/未处理的 MDA-MB-231 细胞中存在持续释放的 IL6、IL8、纤溶酶原激活物抑制剂 1 和 TIMP1/2 的主要表达谱。用 TNFα（40ng/ml）处理对许多这些分子没有影响，只有 CCL2 的释放显著增加（约 1300 倍上调）。亚致死浓度的 DADS（100μM）逆转了 TNFα 诱导的 CCL2 释放，这在抗体检测中是明显的。这些发现为大蒜成分通过免疫调节具有另一种抗癌/化学预防特性提供了证据。
