Chlorhexidine Dihydrochloride Shows Anti-tumor Effects in Desmoid Tumors and Colorectal Cancer
Hyeran Shin1,2, Yonghyo Kim1, Yehyeong Lee1,3
1Drug Discovery Platform Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.
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.
Insights
Chlorhexidine dihydrochloride (CD) effectively inhibited desmoid tumor (DT) and colorectal cancer (CRC) cell growth, migration, and colony formation. This compound shows promise as a novel therapeutic agent for both aggressive fibromatosis and CRC.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Desmoid tumors (DTs), or aggressive fibromatosis, are rare, locally invasive connective tissue neoplasms with limited treatment options and high recurrence rates.
- The need for novel therapeutic strategies for DTs and colorectal cancer (CRC) is significant due to current treatment limitations.
Purpose of the Study:
- To investigate the efficacy of chlorhexidine dihydrochloride (CD) in inhibiting the growth of desmoid tumors (DTs) and colorectal cancer (CRC).
Main Methods:
- Utilized an Apc1638N/+ mouse model for DT studies and collected desmoid tumor cells (DTA) for in vitro analysis.
- Assessed CD's effects on DTA, CRC cell line (HCT-116), and tumor organoids via cell viability, colony formation, and migration assays.
- Evaluated apoptosis induction using caspase 3/7 activity assays and immunoblot analysis, and tested in vivo anti-tumor efficacy in a CRC xenograft model.
Main Results:
- CD significantly inhibited DTA and CRC cell viability, migration, and colony formation in vitro.
- CD demonstrated remarkable reduction in tumor growth in organoids derived from the Apc1638N/+ mouse model.
- CD exhibited significant anti-tumor effects in an in vivo HCT-116 CRC xenograft model.
Conclusions:
- Chlorhexidine dihydrochloride (CD) emerges as a promising therapeutic candidate for both desmoid tumors and colorectal cancer.
- Further research into CD's mechanisms and clinical application for DTs and CRC is warranted.
