Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India.
Department of Zoology, University of Madras, Guindy Campus, Chennai, India.
J Biochem Mol Toxicol. 2020 Feb;34(2):e22433. doi: 10.1002/jbt.22433. Epub 2020 Jan 9.
Colorectal cancer (CRC) is the third most common fatal cancer. Indomethacin, a nonsteroidal anti-inflammatory drug, is known to reduce the occurrence of CRC. This study evaluated the potential anticolon cancer effects of juglone (5-hydroxy-1,4-naphthoquinone) in combination with indomethacin. Human colon adenocarcinoma cells (HT29) were subjected to treatment with indomethacin, juglone, and a combination of both. Morphological analysis, cell cycle regulation, and dual staining using acridine orange and ethidium bromide in control and treated cells revealed the apoptotic potential of these compounds. Bcl2 and inflammatory molecules (tumor necrosis factor-α, nuclear factor kappa B, and Cox-2) were found to be decreased with a concomitant increase in the expression of proapoptotic molecules (Bad, Bax, cytochrome c, and PUMA) as a result of the molecular regulation of Wnt, Notch, and peroxisome proliferator-activated receptor-γ signaling. Treatment with juglone was not as effective as with indomethacin; however, a combination of both was shown to be more effective, suggesting that juglone may be considered for therapeutic intervention of colon cancer.
结直肠癌（CRC）是第三大常见致命癌症。已知非甾体抗炎药吲哚美辛可降低 CRC 的发生。本研究评估了胡桃醌（5-羟基-1,4-萘醌）与吲哚美辛联合应用的潜在抗结肠癌作用。将人结肠腺癌细胞（HT29）用吲哚美辛、胡桃醌和两者的组合进行处理。用吖啶橙和溴化乙锭对对照和处理细胞进行双重染色的形态分析、细胞周期调控揭示了这些化合物的凋亡潜力。结果表明，Bcl2 和炎症分子（肿瘤坏死因子-α、核因子 kappa B 和 Cox-2）的表达降低，同时促凋亡分子（Bad、Bax、细胞色素 c 和 PUMA）的表达增加，这是 Wnt、Notch 和过氧化物酶体增殖物激活受体-γ信号转导的分子调节所致。胡桃醌的治疗效果不如吲哚美辛，但两者的联合使用效果更好，这表明胡桃醌可能被考虑用于结肠癌的治疗干预。
