Hikisz Pawel, Wawrzyniak Piotr, Adamus-Grabicka Angelika A, Jacenik Damian, Budzisz Elzbieta
Department of Oncobiology and Epigenetics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland.
Int J Mol Sci. 2024 Dec 3;25(23):12985. doi: 10.3390/ijms252312985.
The primary objective of this study was to evaluate the anticancer activity of six flavanone/chromanone derivatives: -benzylideneflavanones/-benzylidenechroman-4-ones and their -spiro--pirazolines analogs. We employed five colon cancer cell lines with varying degrees of metastasis and genetic profiles as our research model. Our investigation focused primarily on assessing the pro-oxidant properties of the tested derivatives and their impact on overall antiproliferative activity. To comprehensively evaluate the cytotoxic properties of these compounds, we analyzed their genotoxic, pro-apoptotic, and autophagy-inducing effects. Our findings indicate that three of the six analyzed derivatives exhibited promising antiproliferative activity against cancer cells, with IC values ranging from 10 to 30 μM. Strong pro-oxidant properties were identified as a key mechanism underlying their cytotoxic activity. The generation of oxidative stress, which varied depending on the specific flavanone/chromanone derivative, resulted from increased intracellular reactive oxygen species (ROS) levels and decreased glutathione (GSH) concentrations. Furthermore, oxidative stress likely contributed to the induction of apoptosis/autophagy in cancer cells and the emergence of significant DNA damage.
本研究的主要目的是评估六种黄烷酮/色满酮衍生物：-亚苄基黄烷酮/-亚苄基色满-4-酮及其-螺-吡唑啉类似物的抗癌活性。我们采用了五种具有不同转移程度和基因特征的结肠癌细胞系作为研究模型。我们的研究主要集中在评估受试衍生物的促氧化特性及其对整体抗增殖活性的影响。为了全面评估这些化合物的细胞毒性特性，我们分析了它们的遗传毒性、促凋亡和自噬诱导作用。我们的研究结果表明，六种分析的衍生物中有三种对癌细胞表现出有前景的抗增殖活性，IC值范围为10至30μM。强促氧化特性被确定为其细胞毒性活性的关键机制。氧化应激的产生因特定的黄烷酮/色满酮衍生物而异，是由于细胞内活性氧（ROS）水平升高和谷胱甘肽（GSH）浓度降低所致。此外，氧化应激可能导致癌细胞中凋亡/自噬的诱导以及显著DNA损伤的出现。
