Department of Molecular Pharmacology, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Oncology. 2010;78(1):12-9. doi: 10.1159/000287967. Epub 2010 Feb 24.
Cigarette smoke (CS) is the major risk factor for aerodigestive tract cancers such as lung and oral cancers.
In in vitro models of lung and oral cancers, we found D-penicillamine (PenA) to be a most potent protector against CS, both in the absence and presence of saliva (a highly pro-oxidative condition).
The survival rate of lung cancer cells and oral cancer cells was reduced by CS in the absence of saliva by 39-45% (p < 0.01) and by 55-60% (p < 0.01) in the presence of saliva. The addition of 5 mM PenA to cell medium prior to CS exposure limited cell loss to 22-25% only (p < 0.01). Similarly, the iron chelator desferal protected the cells only in the presence of saliva. PenA also protected against a CS-induced increase in carbonyls (oxidized proteins) and decrease in p53 levels (in the presence of saliva) and mitochondrial membrane potential (a hallmark of CS-induced apoptotic cell death). Malfunctioning p53 often characterizes carcinogenesis of CS-induced cancers.
Redox-active iron and copper in pleural fluid and saliva, upon encounter with CS, may be responsible for this carcinogenesis, mediated via alteration of p53 function. Chelation of redox-active metals may be an efficient tool for prevention of CS-induced lung and oral cancers. The superiority of PenA results from its copper-chelating action as well as its antialdehyde and anti-inflammatory capabilities.
香烟烟雾（CS）是呼吸道和消化道癌症（如肺癌和口腔癌）的主要危险因素。
在肺癌和口腔癌的体外模型中，我们发现 D-青霉胺（PenA）是 CS 的最有效保护剂，无论是在无唾液（高度氧化条件）还是有唾液的情况下。
在无唾液的情况下，CS 使肺癌细胞和口腔癌细胞的存活率降低了 39-45%（p<0.01），在有唾液的情况下降低了 55-60%（p<0.01）。在 CS 暴露前将 5 mM PenA 添加到细胞培养基中，仅将细胞损失限制在 22-25%（p<0.01）。同样，铁螯合剂去铁胺仅在有唾液的情况下保护细胞。PenA 还可以防止 CS 诱导的羰基（氧化蛋白）增加和 p53 水平降低（在有唾液的情况下）以及线粒体膜电位降低（CS 诱导的细胞凋亡的标志）。p53 功能失调通常是 CS 诱导癌症发生的特征。
胸腔液和唾液中的氧化还原活性铁和铜，在遇到 CS 时，可能是导致这种致癌作用的原因，这是通过改变 p53 功能介导的。螯合氧化还原活性金属可能是预防 CS 诱导的肺癌和口腔癌的有效工具。PenA 的优越性源自其铜螯合作用以及其抗乙醛和抗炎能力。
