Kluska Magdalena, Juszczak Michał, Wysokiński Daniel, Żuchowski Jerzy, Stochmal Anna, Woźniak Katarzyna
Department of Molecular Genetics , Faculty of Biology and Environmental Protection , University of Lodz , 90-236 Lodz , Poland . Email:
Department of Biochemistry and Crop Quality , Institute of Soil Science and Plant Cultivation , State Research Institute , 24-100 Pulawy , Poland.
Toxicol Res (Camb). 2019 Sep 10;8(6):896-907. doi: 10.1039/c9tx00176j. eCollection 2019 Nov 1.
Bioactive compounds isolated from plants are considered to be attractive candidates for cancer therapy. In this study, we examined the effect of kaempferol, its derivatives, the polyphenol fraction (PF) and an extract (EX) isolated from the aerial parts of Medik. on DNA damage induced by etoposide in human cells. We also studied the effect of these compounds and their combinations on cell viability. The studies were conducted on HL-60 cells and human peripheral blood mononuclear cells (PBMCs). We used the comet assay in the alkaline version to evaluate DNA damage. To examine cell viability we applied the trypan blue exclusion assay. We demonstrated that kaempferol glycoside derivatives isolated from the aerial parts of Medik. reduce DNA damage induced by etoposide in PBMCs, but do not have an impact on DNA damage in HL-60 cells. We also showed that kaempferol induces DNA damage in HL-60 cells and leads to an increase of DNA damage provoked by etoposide. Our data suggest that kaempferol derivatives can be further explored as a potential agent protecting normal cells against DNA damage induced by etoposide. Moreover, kaempferol's ability to induce DNA damage in cancer cells and to increase DNA damage caused by etoposide may be useful in designing and improving anticancer therapies.
从植物中分离出的生物活性化合物被认为是癌症治疗的有吸引力的候选物。在本研究中，我们检测了山奈酚、其衍生物、从Medik地上部分分离出的多酚组分（PF）和提取物（EX）对依托泊苷在人细胞中诱导的DNA损伤的影响。我们还研究了这些化合物及其组合对细胞活力的影响。研究在HL-60细胞和人外周血单个核细胞（PBMC）上进行。我们使用碱性版本的彗星试验来评估DNA损伤。为了检测细胞活力，我们应用了台盼蓝排斥试验。我们证明，从Medik地上部分分离出的山奈酚糖苷衍生物可减少依托泊苷在PBMC中诱导的DNA损伤，但对HL-60细胞中的DNA损伤没有影响。我们还表明，山奈酚可诱导HL-60细胞中的DNA损伤，并导致依托泊苷引发的DNA损伤增加。我们的数据表明，山奈酚衍生物可作为一种潜在的药物进一步探索，以保护正常细胞免受依托泊苷诱导的DNA损伤。此外，山奈酚在癌细胞中诱导DNA损伤以及增加依托泊苷引起的DNA损伤的能力，可能有助于设计和改进抗癌疗法。
