Abstract
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 inflata 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.
Highlights
Introduction iationsColorectal cancer (CRC) is by far the third most common malignant tumor, and it ranks as the second leading cause of death from cancer in the world [1]
The sequence of P6 is rich in lysine residues and shows no resemblance to any known animal-derived anticancer peptides when searched in non-redundant protein databases via the NCBI BLASTP server
In order to further investigate the underlying mechanism of P6-induced apoptosis in HT-29 and DLD-1 cells, we further examined whether P6 induced apoptosis through arousing the mitochondrial pathway
Summary
Colorectal cancer (CRC) is by far the third most common malignant tumor, and it ranks as the second leading cause of death from cancer in the world [1]. CRC deaths have ameliorated over the past few decades on account of headways in both early diagnosis and intervention; long-term declines in mortality have slowed during last five years [2,3]. The five-year survival rate of CRC is higher than 80%; it decreases to approximately 10% at the advanced stages [1]. It is urgent to develop effective anti-CRC agents with low toxicity to effectively treat and prevent the recurrence and metastasis of CRC. The ocean is home to most of the world’s life. Diverse marine organisms live and thrive in an aquatic buffer system despite the many extreme physiologic stresses, such
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