Chlorhexidine Dihydrochloride Shows Anti-tumor Effects in Desmoid Tumors and Colorectal Cancer

Anticancer Res. 2024 Dec;44(12):5435-5443. doi: 10.21873/anticanres.17369.

Abstract

Background/aim: Desmoid tumors (DTs), or aggressive fibromatosis, are rare neoplasms arising from connective tissue, frequently exhibiting local invasiveness. The limited treatment options and high recurrence rates of DTs highlight the need for novel therapeutic strategies. This study investigated the efficacy of chlorhexidine dihydrochloride (CD) in inhibiting the growth of DTs and colorectal cancer (CRC).

Materials and methods: A mouse model with Apc mutations, specifically Apc1638N/+, was generated to study DTs. DT cells (Apc1638N+) (DTA) were collected from the mice for in vitro experiments. DTA were treated with CD, along with a CRC cell line (HCT-116), and tumor organoids derived from Apc1638N/+ mice. The effects of CD were assessed through cell viability assay (WST assay), colony formation assay, and cell migration assay. We tested the induction of cell apoptosis through caspase 3/7 activity assays and immunoblot analysis of cleaved-caspase 3 and cleaved-PARP1. Additionally, CD was tested for its anti-tumor efficacy using an in vivo CRC xenograft model with the HCT-116 cell line.

Results: CD significantly inhibited the viability, migration, and colony formation of DTA and CRC cells. It remarkably decreased the tumor growth in organoids derived from intestinal tumor cells in the Apc1638N/+ mouse model. Furthermore, CD showed anti-tumor effects in an in vivo CRC xenograft model using the HCT-116 cell line.

Conclusion: CD represents a promising therapeutic strategy for treating both DTs and CRC.

Keywords: Desmoid tumors; anti-cancer therapy; anti-tumor therapy; chlorhexidine dihydrochloride; colorectal cancer.

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis* / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chlorhexidine* / pharmacology
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Fibromatosis, Aggressive* / drug therapy
  • Fibromatosis, Aggressive* / pathology
  • HCT116 Cells
  • Humans
  • Mice
  • Mutation
  • Xenograft Model Antitumor Assays

Substances

  • Chlorhexidine
  • Adenomatous Polyposis Coli Protein
  • Antineoplastic Agents