The tumor suppressor proteins p53 and p27 exhibited a significant role in the survival of cells and regulation of cellular division and growth. In majority of the human tumors, particularly in hepatocellular carcinoma, these proteins are inactivated by mutation or deletion, and are considered to predict the pathophysiology related to liver cancer. The present study evaluated the activation of the p53 and p27 pathways as a useful therapeutic tool to attenuate hepatocellular carcinoma. Three undescribed homologous chromanone derivatives, hyrtiosones A-C were isolated from the organic extract of marine demosponge Hyrtios erectus (family Thorectidae). Preliminary bioactivity assessments found that hyrtiosone A exhibited prospective anti-inflammatory (IC₅₀ 1.02-1.86 mM) and antioxidant (IC₅₀ 0.74-0.83 mM) properties. Molecular docking analysis of the hyrtiosones using p53-murine double minute complex revealed lesser docking parameters for hyrtiosone A (binding energy −11.12 kcal mol⁻¹, docking score −12.18 kcal mol⁻¹) thereby attributing its greater bioactivity. Hyrtiosone A was furthermore analyzed for in vitro anticancer activity in hepatocellular carcinoma HepG2 cells. Morphological assessment of hyrtiosone A treated HepG2 cell line by acridine orange/ethidium bromide fluorescence staining revealed greater number of apoptotic cells, and was found to be comparable with the cells treated with the standard doxorubicin. Further the Annexin V-fluorescein isothiocyanate assay of hyrtiosone A treated HepG2 cell line by flow cytometry displayed greater number of early apoptotic cells (51.24%) than that exhibited by the standard (21.45%). Cell cycle distribution analysis showed that hyrtiosone A arrested the S and G2/M phase of cell cycle and upregulate the gene expression of p53 and p27 in hepatocellular carcinoma HepG2 cells.

肿瘤抑制蛋白 p53 和 p27 在细胞存活和细胞分裂和生长的调节中表现出重要作用。在大多数人类肿瘤中，特别是在肝细胞癌中，这些蛋白质因突变或缺失而失活，被认为可以预测与肝癌相关的病理生理学。本研究评估了p53和p27通路的激活作为减轻肝细胞癌的有用治疗工具。三个未描述的同源色满酮衍生物，hyrtiosones AC 是从海洋海绵状海藻（鼩科）的有机提取物中分离出来的。初步生物活性评估发现，hyrtiosone A 表现出预期的抗炎（IC₅₀  1.02-1.86 mM) 和抗氧化剂 (IC ₅₀  0.74-0.83 mM) 特性。使用p53-鼠双微复合物对hyrtiosones的分子对接分析揭示了hyrtiosone A的较小对接参数（结合能-11.12 kcal mol ^-1，对接得分-12.18 kcal mol ^-1），从而归因于其更大的生物活性。进一步分析了 Hyrtiosone A 的体外肝细胞癌 HepG2 细胞的抗癌活性。通过吖啶橙/溴化乙锭荧光染色对羟甲磺酸钠 A 处理的 HepG2 细胞系的形态学评估显示更多数量的凋亡细胞，并且发现与用标准多柔比星处理的细胞相当。此外，通过流式细胞术对羟乙磺酸钠 A 处理的 HepG2 细胞系进行的膜联蛋白 V-异硫氰酸荧光素测定显示出比标准显示的数量更多的早期凋亡细胞 (51.24%) (21.45%)。细胞周期分布分析表明，hyrtiosone A阻滞细胞周期的S期和G2/M期，上调肝癌HepG2细胞中p53和p27的基因表达。