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Solid Lipid Curcumin Particles Induce More DNA Fragmentation and Cell Death in Cultured Human Glioblastoma Cells than Does Natural Curcumin

机译:固体脂质姜黄素颗粒比天然姜黄素在培养的人胶质母细胞瘤细胞中诱导更多的DNA片段化和细胞死亡

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摘要

Despite recent advancements in cancer therapies, glioblastoma multiforme (GBM) remains largely incurable. Curcumin (Cur), a natural polyphenol, has potent anticancer effects against several malignancies, including metastatic brain tumors. However, its limited bioavailability reduces its efficiency for treating GBM. Recently, we have shown that solid lipid Cur particles (SLCPs) have greater bioavailability and brain tissue penetration. The present study compares the efficiency of cell death by Cur and/or SLCPs in cultured GBM cells derived from human (U-87MG) and mouse (GL261) tissues. Several cell viability and cell death assays and marker proteins (MTT assay, annexin-V staining, TUNEL staining, comet assay, DNA gel electrophoresis, and Western blot) were investigated following the treatment of Cur and/or SLCP (25 μM) for 24–72 h. Relative to Cur, the use of SLCP increased cell death and DNA fragmentation, produced longer DNA tails, and induced more fragmented nuclear lobes. In addition, cultured GBM cells had increased levels of caspase-3, Bax, and p53, with decreases in Bcl2, c-Myc, and both total Akt, as well as phosphorylated Akt, when SLCP, rather Cur, was used. Our in vitro work suggests that the use of SLCP may be a promising strategy for reversing or preventing GBM growth, as compared to using Cur.
机译:尽管最近在癌症治疗方面取得了进展,但多形胶质母细胞瘤(GBM)仍在很大程度上无法治愈。姜黄素(Curcumin)是一种天然多酚,对多种恶性肿瘤具有有效的抗癌作用,包括转移性脑瘤。但是,其有限的生物利用度降低了其治疗GBM的效率。最近,我们已经表明,固态脂质Cur颗粒(SLCP)具有更高的生物利用度和脑组织渗透能力。本研究比较了Cur和/或SLCP在源自人(U-87MG)和小鼠(GL261)组织的培养的GBM细胞中的细胞死亡效率。在对Cur和/或SLCP(25μm)处理24后,研究了几种细胞活力和细胞死亡的测定方法和标记蛋白(MTT测定,膜联蛋白-V染色,TUNEL染色,彗星测定,DNA凝胶电泳和Western印迹)。 –72 h。相对于Cur,SLCP的使用增加了细胞死亡和DNA片段化,产生了更长的DNA尾巴,并诱导了更多的核裂片。另外,当使用SLCP而不是Cur时,培养的GBM细胞的caspase-3,Bax和p53的水平升高,而Bcl2,c-Myc和总Akt以及磷酸化的Akt均降低。我们的体外研究表明,与使用Cur相比,使用SLCP可能是逆转或预防GBM增长的有前途的策略。

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