This study investigates the phytochemical composition and anticancer properties of extracts from the marine sponges Haliclona fascigera (HFE) and Stylissa carteri (SCE), collected from the Red Sea coast of Jeddah, Saudi Arabia, against human colorectal cancer cell lines HCT116 and HT-29 employing SRB assay at varying concentrations (ranging from 0.01 to 1000 µg/mL), compared to the positive control doxorubicin (DOX). The RP-HPLC-QTOF-MS and tandem MS/MS revealed the presence of 59 metabolites belonging to several classes that were described for the first time in HFE and SCE with a predominance of nitrogenous compounds. SCE exhibited a markedly more pronounced cytotoxic effect, with IC50 of 1.9 ± 0.04 µg/mL for the HCT-116 cell line and 7.8 ± 0.6 µg/mL for the HT-29 cell line. In contrast, HFE demonstrated higher IC50 values of 46.5 ± 1.3 µg/mL for HCT-116 and 61.9 ± 2.2 µg/mL for HT-29, indicating that SCE is significantly more potent than HFE, particularly in the HCT-116 cell line. Cell cycle analysis indicated that SCE predominantly induces apoptosis in the S-phase, while HFE significantly affects the G2-phase. Flow cytometric analysis demonstrated late apoptosis in both cell lines, with HFE inducing late apoptosis in 88.72 % of HCT-116 cells and 90.50 % of HT-29 cells, while SCE induced late apoptosis in 58.36 % of HCT-116 cells and 72.22 % of HT-29 cells. Treatment with HFE and SCE led to significant downregulation of the anti-apoptotic gene Bcl-Xl in both HCT116 and HT-29 cells, with HFE showing the strongest effect, especially in HT-29 cells (0.10-fold change). For the pro-apoptotic p53 gene, both extracts increased expression levels, with HFE yielding the highest upregulation in HCT116 cells (1.51-fold change). This suggests that these sponge extracts promote apoptosis by decreasing anti-apoptotic signalling while enhancing pro-apoptotic pathways, potentially aiding in cancer cell viability reduction.The study evaluates the binding affinities of various compounds against Bcl-2, Human Survivin, and KRAS p.G12C, which are key targets in colorectal cancer. Eicosanamide exhibited the highest binding affinities, outperforming both the co-crystallized ligands and Doxorubicin in several cases, making it a promising candidate for further investigation. Hyptolide and Palmitic Acid also showed significant potential, especially against KRAS p.G12C and Bcl-2, indicating their potential as multi-target inhibitors in colorectal cancer therapy. These findings indicate that both sponge extracts possess promising anticancer properties, with SCE being a particularly potent candidate for further investigation and potential therapeutic applications.
扫码关注我们
求助内容:
应助结果提醒方式:
