Anticancer activity of Helicobacter pylori ribosomal protein (HPRP) with iRGD in treatment of colon cancer

J Cancer Res Clin Oncol. 2021 Oct;147(10):2851-2865. doi: 10.1007/s00432-021-03683-7. Epub 2021 Jun 12.

Abstract

Purpose: As the conventional therapeutic approaches were not completely successful in the treatment of colon cancer, there is still a need for finding the most efficient therapeutic agents. Here we investigated the anticancer activity of HPRP-A1 that was derived from the N-terminal region of Helicobacter pylori ribosomal protein L1 (RpL1) alone or in combination with tumor-homing peptide iRGD and 5-Fluorouracil (5FU) on colon cancer cell lines (CT26 and HT29) and isograft models of colon cancer.

Method: We assessed the tumor growth inhibitory activity of HPRP-A1 with or without iRGD and 5FU on colon cancer in vitro and in vivo. In the in vitro part, we investigate the effect of HPRP-A1 alone and in combination with iRGD/5FU.

Results: Our results demonstrated that co-administration of HPRP-A1 with iRGD increased the apoptosis, while these two peptides in combination with 5FU increased the intracellular level of p53 that upregulate the pro-apoptotic gene BAX and downregulate the anti-apoptotic gene BCL2. HPRP-A1 blocks the cell cycle progression in G0/G1. Co-administration of two peptides significantly reduced the size and weight of the tumors, while the group that received 5FU in combination with the peptides increased the necrotic and decrease the fibrotic area significantly in the tumor tissues, which also disrupt the oxidant/antioxidant balance.

Conclusions: Our results indicated that HPRP-A1 could be considered an effective agent toward colon cancer in vitro and in vivo with the ability to enhance the effects of conventional chemotherapy agent 5FU.

Keywords: Bacterial peptide; Colon cancer; HPRP-A1; iRGD.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Apoptosis
  • Bacterial Proteins / administration & dosage*
  • Bacterial Proteins / metabolism
  • Cell Movement
  • Cell Proliferation
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Drug Therapy, Combination
  • Female
  • Fluorouracil / pharmacology*
  • Helicobacter pylori / metabolism
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oligopeptides / pharmacology*
  • Ribosomal Proteins / administration & dosage*
  • Ribosomal Proteins / metabolism
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antimetabolites, Antineoplastic
  • Bacterial Proteins
  • N-end cysteine peptide tumor-homing peptide
  • Oligopeptides
  • Ribosomal Proteins
  • Fluorouracil