A Novel Peptide Derived from Arca inflata Induces Apoptosis in Colorectal Cancer Cells through Mitochondria and the p38 MAPK Pathway

• Published in: Marine drugs Vol. 20; no. 2; p. 110
• Main Authors: Li, Chunlei, Zhang, Sirui, Zhu, Jianhua, Huang, Weijuan, Luo, Yuanyuan, Shi, Hui, Yu, Dongbo, Chen, Liguo, Song, Liyan, Yu, Rongmin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.01.2022; MDPI
• Subjects: Amino acid sequence; Amino acid sequences; Amino acids; Analytical methods; Animals; Anticancer properties; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Antitumor activity; antitumor peptide; Antitumour agents; Apoptosis; Apoptosis - drug effects; Arca inflata; Arcidae - chemistry; Binding sites; calmodulin; Cancer; Cell activation; Cell cycle; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cells; Chemical compounds; Circular Dichroism; Colon; Colon cancer; Colonies; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Cyanobacteria; Cytotoxicity; Dichroism; DNA; Flow cytometry; Herbal medicine; HT29 Cells; Humans; Male; MAP kinase; MAPK signaling; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Molecular weight; Neoplasms; Nucleotide sequence; p38 Mitogen-Activated Protein Kinases - metabolism; Peptides - chemistry; Peptides - isolation & purification; Peptides - pharmacology; Pharmacology; Polypeptides; Proliferation; Protein structure; Secondary structure; Signal transduction; Spectroscopy; Spectrum analysis; Transcriptomics; Tumors; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation; China; apoptosis; Arca inflata; colorectal cancer; calmodulin; antitumor peptide; MAPK signaling
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md20020110

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, Reeve. 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.