Ghorbani Arman, Zand Hamid, Jeddi-Tehrani Mahmood, Koohdani Fariba, Shidfar Farzad, Keshavarz Seyed Ali
Cellular and Molecular Nutrition Department, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
J Nat Med. 2015 Oct;69(4):507-12. doi: 10.1007/s11418-015-0915-7. Epub 2015 May 1.
The bioactive components of dietary phytochemicals are in the spotlight of research institutes, due to their significant antioxidant activities and health-promoting properties. Resveratrol is a polyphenol which is found abundantly in grapes and berries and has long been known as a chemo-preventive agent. The main purpose of this study was to provide a new mechanistic insight into the growth inhibition of acute lymphoblastic leukemia cells by resveratrol along with a DNA damage agent. It was found that the treatment of pre-B ALL cells by resveratrol in the presence or absence of doxorubicin resulted in decreased cell viability and a synergistic increase in cytotoxicity. Cell death was accompanied by a significant increase in phosphorylated p53 at serine 15 and accumulation of PTEN. In addition, resveratrol inhibited the over-expression of p-AKT and p-ERK1/2. These findings clearly demonstrated that resveratrol and doxorubicin synergistically increase the cytotoxicity of pre-B ALL cells via the hyper-activation of two important tumor suppressor proteins and two major signal transduction pathways.
由于其显著的抗氧化活性和促进健康的特性,膳食植物化学物质的生物活性成分成为了研究机构的关注焦点。白藜芦醇是一种在葡萄和浆果中大量存在的多酚,长期以来一直被认为是一种化学预防剂。本研究的主要目的是为白藜芦醇与一种DNA损伤剂联合抑制急性淋巴细胞白血病细胞生长提供新的机制见解。研究发现,无论是否存在阿霉素,用白藜芦醇处理前B急性淋巴细胞白血病细胞都会导致细胞活力下降和细胞毒性协同增加。细胞死亡伴随着丝氨酸15处磷酸化p53的显著增加和PTEN的积累。此外,白藜芦醇抑制了p-AKT和p-ERK1/2的过度表达。这些发现清楚地表明,白藜芦醇和阿霉素通过两种重要的肿瘤抑制蛋白和两条主要信号转导途径的过度激活,协同增加了前B急性淋巴细胞白血病细胞的细胞毒性。