Homoisoflavanone Delays Colorectal Cancer Progression via DNA Damage-Induced Mitochondrial Apoptosis and...

Area of Science:

• Natural Product Chemistry
• Cancer Biology
• Pharmacology

Background:

• Colorectal cancer (CRC) presents a significant global health burden, with advanced stages exhibiting limited therapeutic responses.
• Herbal medicines are a rich source of novel anticancer compounds, offering alternative therapeutic strategies.
• Polygonatum kingianum is a traditional medicinal herb with potential pharmacological activities.

Purpose of the Study:

• To isolate and characterize a bioactive homoisoflavanone from Polygonatum kingianum.
• To evaluate the in vitro and in vivo anticancer efficacy of the isolated homoisoflavanone against colorectal cancer.
• To elucidate the underlying molecular mechanisms of homoisoflavanone-induced colorectal cancer cell death.

Main Methods:

• Isolation and structural elucidation of homoisoflavanone from Polygonatum kingianum.
• In vitro antiproliferative and apoptosis assays using colorectal cancer cell lines.
• In vivo tumor growth inhibition studies in a colorectal cancer xenograft mouse model.
• Mechanistic studies involving DNA damage, mitochondrial function, reactive oxygen species (ROS), and ATP levels.
• Immunohistochemical analysis of tumor tissues.

Main Results:

• A novel homoisoflavanone was successfully isolated and characterized from Polygonatum kingianum.
• In vitro, homoisoflavanone demonstrated significant antiproliferative and pro-apoptotic activity in colorectal cancer cells.
• Homoisoflavanone induced DNA damage, mitochondrial apoptosis, parthanatos-like cell death, and activated the ATM/ATR-Chk1 pathway.
• In vivo, homoisoflavanone suppressed tumor growth in a colorectal cancer xenograft model without observable systemic toxicity.
• Immunohistochemistry confirmed reduced proliferation and increased apoptosis and parthanatos-like cell death in treated tumors.

Conclusions:

• Homoisoflavanone from Polygonatum kingianum is a potent anticancer agent against colorectal cancer.
• The compound exerts its effects by inducing DNA damage and disrupting mitochondrial homeostasis, leading to multiple cell death pathways.
• Homoisoflavanone represents a promising lead compound for the development of novel anticancer therapeutics derived from herbal medicines.