Anticancer activity of Pseudomonas aeruginosa derived peptide with iRGD in colon cancer therapy

Abstract

Objectives: Colon cancer is well-known as a life-threatening disease. Since the current treatment modalities for this type of cancer are powerful yet face some limitations, finding novel treatments is required to achieve better outcomes with fewer side effects. Here we investigated the therapeutic potential of Azurin-p28 alone or along with iRGD (Ac-CRGDKGPDC-amide) as a tumor-penetrating peptide and 5-fluorouracil (5-FU) for colon cancer.

Materials and methods: Inhibitory effect of p28 with or without iRGD/5-FU was studied in CT26 and HT29, as well as the xenograft animal model of cancer. The effect of p28 alone or along with iRGD/5-FU on cell migration, apoptotic activity, and cell cycle of the cell lines was assessed. Level of the BAX and BCL2 genes, tumor suppressor genes [(p53 and collagen type-Iα1 (COL1A1), collagen type-Iα2 (COL1A2)] were assessed by quantitative RT-PCR.

Results: These findings show that using p28 with or without iRGD and 5-FU raised the level of p53 and BAX but decreased BCL2, compared with control and 5-FU groups in tissues of the tumor, which result in raising the apoptosis.

Conclusion: It seems that p28 may be used as a new therapeutic approach in colon cancer therapy that can enhance the anti-tumor effect of 5-FU.

Keywords: Azurin-p28; Bacterial peptide; Colon cancer; Irgd; Pseudomonas aeruginosa.

Figure 1

A: Schematic representation of the experimental methodology and mouse colon model; B: Workflow

Figure 2

IC₅₀ values for the peptide-treated L929, CT26, and HT29 cells

Figure 3

Ability of peptides to cause apoptosis in cancer cell lines

Figure 4

Shows how colon cancer cell lines’ cell cycles are affected by p28

Figure 5

Shows how p28 prevents colon cancer cells from migrating and encroaching

Figure 6

shows how p28, either alone or in combination with iRGD and 5-FU, inhibits the development of CT26 cells in xenograft nude mice

Figure 7

Shows microscopic findings from the xenograft mouse model showing necrosis and its impact on organs

Figure 8

Trichrome staining shows the presence of fibrotic tissue and an increase of collagen in tumor tissue

Figure 9

Shows the impact of p28 on indicators of oxidative, cytokines of inflammation, as well as genes that promote fibrosis