Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland.
Department of Physiology in Health Sciences, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland.
Molecules. 2023 Jul 8;28(14):5292. doi: 10.3390/molecules28145292.
Rhabdomyosarcoma (RMS) is a malignant tumour of the soft tissues. There are two main histopathological types: alveolar and embryonal. RMS occurs mainly in childhood and is a result of the deregulation of growth and differentiation of muscle cell precursors. There is an increasing amount of data indicating that numerous epigenetic alterations within chromatin and histone proteins are involved in the pathogenesis of this malignancy. Histone acetylation is one of the most important epigenetic modifications that is catalysed by enzymes from the group of histone acetyltransferases (HAT). In this study, the impact of the natural histone acetyltransferase inhibitors (HATi)-garcinol (GAR) and anacardic acid (AA)-on the biology of RMS cells was evaluated through a series of in vitro tests measuring proliferation, viability, clonogenicity, cell cycle and apoptosis. Moreover, using oligonucleotide microarrays and real-time PCR, we identified several genes whose expression changed after GAR and AA treatment. The examined HATi significantly reduce the invasive phenotype of RMS cells by inhibiting the growth rate, viability and clonogenic abilities. What is more, these substances cause cell cycle arrest in the G2/M phase, induce apoptosis and affect the genetic expression of the endoplasmic reticulum stress sensors. GAR and AA may serve as promising potential anti-cancer drugs since they sensitize the RMS cells to chemotherapeutic treatment.
横纹肌肉瘤（RMS）是一种软组织恶性肿瘤。有两种主要的组织病理学类型：肺泡和胚胎型。RMS 主要发生在儿童时期，是肌肉细胞前体生长和分化失调的结果。越来越多的数据表明，染色质和组蛋白蛋白内的许多表观遗传改变参与了这种恶性肿瘤的发病机制。组蛋白乙酰化是最重要的表观遗传修饰之一，由组蛋白乙酰转移酶（HAT）组中的酶催化。在这项研究中，通过一系列体外试验，评估了天然组蛋白乙酰转移酶抑制剂（HATi）-garcinol（GAR）和 anacardic acid（AA）对 RMS 细胞生物学的影响，这些试验测量了增殖、活力、集落形成能力、细胞周期和细胞凋亡。此外，使用寡核苷酸微阵列和实时 PCR，我们鉴定了 GAR 和 AA 处理后表达发生变化的几个基因。这些被检测到的 HATi 通过抑制 RMS 细胞的生长速度、活力和集落形成能力显著降低了其侵袭表型。更重要的是，这些物质导致细胞周期停滞在 G2/M 期，诱导细胞凋亡，并影响内质网应激传感器的基因表达。GAR 和 AA 可能作为有前途的潜在抗癌药物，因为它们使 RMS 细胞对化疗敏感。
