Colorectal carcinoma (CRC) is one of the major causes of cancer-related incidence and deaths. Here, we identified a novel antitumor peptide, P6, with a molecular weight of 2794.8 Da from a marine Chinese medicine,Arca inflataReeve. The full amino acid sequence and secondary structure of P6 were determined by tandem mass de novo sequencing and circular dichroism spectroscopy, respectively. P6 markedly inhibited cell proliferation and colony formation, and induced apoptosis in CRC cells. Mechanistically, transcriptomics analysis and a serial functional evaluation showed that P6 induced colon cancer cell apoptosis through the activation of the p38-MAPK signaling pathway. Moreover, it was demonstrated that P6 exhibited antitumor effects in a tumor xenograft model, and induced cell cycle arrest in CRC cells in a concentration-dependent mode. These findings provide the first line of indication that P6 could be a potential therapeutic agent for CRC treatment.Keywords:Arca inflata;antitumor peptide;apoptosis;MAPK signaling;calmodulin;colorectal cancer
Chunlei Li,Weijuan Huang,Hang Zheng,Hui Shi,Sixue Bi,Liyan Song,Jianhua Zhu,Rongmin Yu,Yurong Wang
A novel acidic homogeneous polysaccharide (AIPW50-1) with a molecular weight of 214.5 kDa was isolated by hot water extraction and several column chromatographic purification methods from Arca inflata Reeve. The repeating structural units of AIPW50-1 were elucidated by the combined chemical and instrumental analyses. AIPW50-1 is composed of glucose, glucuronic acid and galactose with molar ratio of 18.06: 1.00: 1.56. The backbone of AIPW50-1 consisted of →4)-α-D-GlcpA-(1→, →4)-α-D-Glcp-(1→ and →4,6)-α-D-Glcp-(1→ with two branches of α-D-Glcp-(1→ and →6)-β-D-Galp-(1→ terminated with α-D-Glcp-(1→, respectively. The antioxidant assay demonstrated that AIPW50-1 possessed strong ABTS free radical scavenging activity and prominently stimulated the secretion of a cytotoxic molecule (NO), cytokines (TNF-α and IL-6) by murine RAW 264.7 macrophages. The in vivo antioxidative effect of AIPW50-1 was further evaluated using Caenorhabdiyis elegans oxidative stress model. AIPW50-1 could prolong the lifespan, improve locomotory behavior and reproductive ability, and significantly enhance intracellular activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of C. elegans by 19.80 %, 17.05 % and 17.22 % at 4 mg/mL. These results suggested that AIPW50-1 has the potential to be used as a functional additive with antioxidant and immunomodulatory effects.
危险品化学品经营许可证（带存储）