Drzewiecka Małgorzata, Jaśniak Dominika, Barszczewska-Pietraszek Gabriela, Czarny Piotr, Kobrzycka Anna, Wieczorek Marek, Radek Maciej, Szemraj Janusz, Skorski Tomasz, Śliwiński Tomasz
Laboratory of Medical Genetics Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
Department of Medical Biochemistry, Medical University of Lodz, 92-216 Lodz, Poland.
J Pers Med. 2023 Aug 27;13(9):1315. doi: 10.3390/jpm13091315.
HDAC inhibitors (HDACi) hold great potential as anticancer therapies due to their ability to regulate the acetylation of both histone and non-histone proteins, which is frequently disrupted in cancer and contributes to the development and advancement of the disease. Additionally, HDACi have been shown to enhance the cytotoxic effects of DNA-damaging agents such as radiation and cisplatin. In this study, we found that histone deacetylase inhibits valproic acid (VPA), synergized with PARP1 inhibitor (PARPi), talazoparib (BMN-673), and alkylating agent, and temozolomide (TMZ) to induce DNA damage and reduce glioblastoma multiforme. At the molecular level, VPA leads to a downregulation of FANCD2 and RAD51, and the eradication of glioblastoma cells. The results of this study indicate that combining HDACi with PARPi could potentially enhance the treatment of glioblastoma, the most aggressive type of cancer that originates in the brain.
组蛋白去乙酰化酶抑制剂（HDACi）作为抗癌疗法具有巨大潜力，因为它们能够调节组蛋白和非组蛋白的乙酰化，而这种乙酰化在癌症中经常被破坏，并促进疾病的发展和进展。此外，HDACi已被证明可增强辐射和顺铂等DNA损伤剂的细胞毒性作用。在本研究中，我们发现组蛋白去乙酰化酶抑制剂丙戊酸（VPA）与聚（ADP-核糖）聚合酶1抑制剂（PARPi）他拉唑帕尼（BMN-673）以及烷化剂替莫唑胺（TMZ）协同作用，可诱导DNA损伤并减少多形性胶质母细胞瘤。在分子水平上，VPA导致范可尼贫血互补组D2（FANCD2）和RAD51下调，并根除胶质母细胞瘤细胞。本研究结果表明，将HDACi与PARPi联合使用可能会增强对胶质母细胞瘤的治疗效果，胶质母细胞瘤是起源于大脑的最具侵袭性的癌症类型。
