Indomethacin and juglone inhibit inflammatory molecules to induce apoptosis in colon cancer cells
Alagesan Seetha, Halagowder Devaraj, Ganapasam Sudhandiran
Abstract
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.