Guerra Fabiana Sélos, Rodrigues Daniel Alencar, Fraga Carlos Alberto Manssour, Fernandes Patricia Dias
Laboratório de Farmacologia da Dor e da Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, Brazil.
Programa de Pós-graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, Brazil.
Pharmaceuticals (Basel). 2021 Apr 21;14(5):387. doi: 10.3390/ph14050387.
Prostate cancer is the second most frequently diagnosed malignancy worldwide. Here, the cytotoxic and antimetastatic effects of a new HDAC6/8 inhibitor, LASSBio-1911, and a new dual-PI3K/HDAC6 inhibitor, LASSBio-2208, were evaluated against PC3 prostate cancer cell line.
A MTT assay was used to assess the cell viability. Annexin V/propidium iodide (PI) was used to detect apoptotic cell death and to analyze the cell cycle distribution. Interleukin 6 (IL-6) levels were measured by ELISA. A cell scratch assay was performed to assess cell migration, and the expression of proteins was estimated by Western blotting.
LASSBio-1911 and LASSBio-2208 exert cytotoxic effects against PC3 cells. However, LASSBio-2208 was demonstrated to be more potent than LASSBio-1911. The apoptosis assays showed that both compounds trigger apoptotic processes and cause the arrest of cells in the G2/M phase of the cell cycle. The Western blot analysis revealed that LASSBio-2208 significantly decreased the expression of p-JNK and JAK2. However, both compounds reduced the expression of p-STAT3, IL-6 secretion, and cell migration.
LASSBio-1911 and LASSBio-2208 demonstrated significant activity in reducing cell viability and migration. These compounds can be further used as prototypes for the development of new potential anticancer alternative treatments.
前列腺癌是全球第二常见的确诊恶性肿瘤。在此，评估了一种新型HDAC6/8抑制剂LASSBio-1911和一种新型双PI3K/HDAC6抑制剂LASSBio-2208对PC3前列腺癌细胞系的细胞毒性和抗转移作用。
采用MTT法评估细胞活力。用膜联蛋白V/碘化丙啶（PI）检测凋亡细胞死亡并分析细胞周期分布。通过酶联免疫吸附测定法测量白细胞介素6（IL-6）水平。进行细胞划痕试验以评估细胞迁移，并通过蛋白质印迹法估计蛋白质的表达。
LASSBio-1911和LASSBio-2208对PC3细胞具有细胞毒性作用。然而，已证明LASSBio-2208比LASSBio-1911更有效。凋亡试验表明，这两种化合物均触发凋亡过程并导致细胞在细胞周期的G2/M期停滞。蛋白质印迹分析显示，LASSBio-2208显著降低p-JNK和JAK2的表达。然而，这两种化合物均降低了p-STAT3的表达、IL-6分泌和细胞迁移。
LASSBio-1911和LASSBio-2208在降低细胞活力和迁移方面表现出显著活性。这些化合物可进一步用作开发新的潜在抗癌替代疗法的原型。
