Chlorogenic acid induces apoptosis and cell-cycle arrest in colorectal cancer cells

Mol Biol Rep. 2023 Dec;50(12):9845-9857. doi: 10.1007/s11033-023-08854-y. Epub 2023 Oct 17.

Abstract

Background: Apoptotic agents from natural products like phenolic compounds can be used effectively in the treatment of cancer. Chlorogenic acid (CGA) is one of the phenolic compounds in medicinal plants with anti-cancer properties. In this research, we aimed to explore the anti-cancer mode of action of CGA on colorectal cancer (CRC) cells in vitro conditions.

Methods: HT-29 and HEK-293 cells were cultured after MTT assay for 24 h with CGA 100 µM, and without CGA. Then, flow cytometry assays and the expression of apoptosis-related genes including caspase 3 and 9, Bcl-2 and Bax, and cell cycle-related genes including P21, P53 and NF-κB at mRNA and protein levels were examined. Finally, we measured the amount of intracellular reactive oxygen species (ROS).

Results: The cell viability of all two-cell lines decreased in a dose-dependent manner. Moreover, CGA induces cell cycle arrest in HT-29 cells by increasing the expression of P21 and P53. It also induces apoptosis in HT-29 cells by mitigating Bcl-2 and NF-κB expression and elevating caspase 3 and 9 expression and ROS levels.

Conclusions: Considering the cytotoxicity and cell cycle arrest and induction of apoptosis in the colon cancer cell line by CGA, it can be concluded that CGA is a suitable option for the treatment of colon cancer.

Keywords: Caspase 9; Cell cycle; HEK-293; HT-29 cells; P21; ROS.

MeSH terms

  • Apoptosis
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Chlorogenic Acid / pharmacology
  • Colonic Neoplasms* / metabolism
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • HEK293 Cells
  • Humans
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Chlorogenic Acid
  • Caspase 3
  • Reactive Oxygen Species
  • NF-kappa B
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-bcl-2