舒林酸增强了对暴露于氧化应激下癌细胞的杀伤作用。

Sulindac enhances the killing of cancer cells exposed to oxidative stress.

作者信息

Marchetti Maria, Resnick Lionel, Gamliel Edna, Kesaraju Shailaja, Weissbach Herbert, Binninger David

机构信息

Center for Molecular Biology and Biotechnology, Florida Atlantic University, Boca Raton, Florida, United States of America.

出版信息

PLoS One. 2009 Jun 5;4(6):e5804. doi: 10.1371/journal.pone.0005804.

BACKGROUND

Sulindac is an FDA-approved non-steroidal anti-inflammatory drug (NSAID) that affects prostaglandin production by inhibiting cyclooxygenases (COX) 1 and 2. Sulindac has also been of interest for more than decade as a chemopreventive for adenomatous colorectal polyps and colon cancer.

PRINCIPAL FINDINGS

Pretreatment of human colon and lung cancer cells with sulindac enhances killing by an oxidizing agent such as tert-butyl hydroperoxide (TBHP) or hydrogen peroxide. This effect does not involve cyclooxygenase (COX) inhibition. However, under the conditions used, there is a significant increase in reactive oxygen species (ROS) within the cancer cells and a loss of mitochondrial membrane potential, suggesting that cell death is due to apoptosis, which was confirmed by Tunel assay. In contrast, this enhanced killing was not observed with normal lung or colon cells.

SIGNIFICANCE

These results indicate that normal and cancer cells handle oxidative stress in different ways and sulindac can enhance this difference. The combination of sulindac and an oxidizing agent could have therapeutic value.

背景

舒林酸是一种经美国食品药品监督管理局（FDA）批准的非甾体抗炎药（NSAID），它通过抑制环氧化酶（COX）1和2来影响前列腺素的生成。在过去十多年里，舒林酸作为一种预防腺瘤性结直肠息肉和结肠癌的化学预防剂也备受关注。

主要发现

用舒林酸预处理人结肠癌细胞和肺癌细胞可增强氧化剂（如叔丁基过氧化氢（TBHP）或过氧化氢）的杀伤作用。这种作用不涉及环氧化酶（COX）抑制。然而，在所使用的条件下，癌细胞内活性氧（ROS）显著增加，线粒体膜电位丧失，提示细胞死亡是由凋亡所致，这通过Tunel检测得以证实。相比之下，正常肺细胞或结肠细胞未观察到这种增强的杀伤作用。