Anticancer activity and radiosensitization effect of methyleneisoxazolidin-5-ones in hepatocellular carcinoma HepG2 cells. (25th March 2016)

• Record Type: Journal Article
• Authors: Gach, Katarzyna; Grądzka, Iwona; Wasyk, Iwona; Męczyńska-Wielgosz, Sylwia; Iwaneńko, Teresa; Szymański, Jacek; Koszuk, Jacek; Janecki, Tomasz; Kruszewski, Marcin; Janecka, Anna
• Is Part Of: Chemico-biological interactions. Volume 248(2016)
• Page Start: 68
• Page End: 73
• Publication Date: 2016-03-25
• Subjects: Anticancer agents -- Apoptosis -- HepG2 -- Integrated therapy -- X-ray sensitization; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2016.01.011
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Parthenolide (PTL), a well-known sesquiterpene lactone of natural origin with α, β-unsaturated carbonyl structure, has proven to show promising anti-cancer properties. In this report, anti-proliferative potential of two synthetic methyleneisoxazolidin-5-ones, MZ-6 and MZ-14, with the same structural motif, has been investigated in human hepatoma HepG2 cells. The effects on apoptosis induction and DNA damage were evaluated. All compounds decreased the number of live cells and increased the number of late apoptotic cells. However, only MZ-14 was able to induce DNA damage. Both synthetic compounds increased intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential changes at the same level as PTL. Additionally, cell survival was analyzed after a combined treatment, in which HepG2 cells were preincubated for 24 h with MZ-6, MZ-14 or PTL and irradiated with different doses of X-rays. The inhibition of cell survival was assessed by the clonogenic assay. We have shown that the clone formation was strongly inhibited by the combined treatment. The synergistic effect was observed for all three compounds but MZ-6 was significantly more effective. It is interesting to note that in HepG2 cells MZ-6 was the least cytotoxic of the tested compounds, did not induce DNA damage and was less active than the others in the clonogenic cell survival assay. It seems advantages from the point of view of the further in vivo studies that the compound with the lowest cytotoxic activity showed the strongest sensitizing effect. Highlights: Anticancer activity of two methyleneisoxazolidin-5-ones was tested in HepG2 cells. Synthetic compounds induced apoptosis through ROS generation. Pretreatment with the tested compounds sensitized the HepG2 cells to X-radiation.