Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Kaempferol in Colorectal Cancer Cells.

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Human colorectal carcinoma (hCRC) is a prevalent cancer with significant latency.
• Dietary supplements show promise in cancer treatment.
• Kaempferol is a natural flavonoid with known anticancer properties.

Purpose of the Study:

• To investigate the anti-proliferative effects of Kaempferol on hCRC.
• To elucidate the molecular mechanisms underlying Kaempferol's action in hCRC.

Main Methods:

• HPLC and UV-Vis spectroscopy assessed Kaempferol stability.
• Confocal microscopy determined Kaempferol cellular localization.
• Anticancer activity was tested on multiple human cancer cell lines, including DLD-1 (hCRC).
• Molecular docking and dynamics simulations analyzed Kaempferol-BcL-2 interactions.

Main Results:

• Kaempferol demonstrated significant anti-proliferative effects on DLD-1 cells (IC50 = 49.55 µM).
• Kaempferol treatment increased endoplasmic reticulum stress and apoptosis by 47%.
• Kaempferol modulated key genes and proteins involved in apoptosis and cancer pathways (BcL-2, Bax, Caspase-3, p53, etc.).
• Molecular simulations confirmed stable binding of Kaempferol to the BcL-2 active site.

Conclusions:

• Kaempferol induces colorectal cancer cell death through ER stress-mediated apoptosis.
• Modulation of BcL-2 is a key mechanism in Kaempferol's anticancer activity.
• Kaempferol shows potential as a therapeutic agent for hCRC, warranting further preclinical investigation.