Synthesis of Bioactive Diarylheptanoids from Alpinia officinarum and Their Mechanism of Action for Anticancer Properties in Breast Cancer Cells.
Sunita GamreMrityunjay TyagiSucheta ChatterjeeBirija Sankar PatroSubrata ChattopadhyayDibakar GoswamiPublished in: Journal of natural products (2021)
An efficient synthesis of the Alpinia officinarum-derived diarylheptanoids, viz., enantiomers of a β-hydroxyketone (1) and an α,β-unsaturated ketone (2) was developed starting from commercially available eugenol. Among these, compound 2 showed a superior antiproliferative effect against human breast adenocarcinoma MCF-7 cells. Besides reducing clonogenic cell survival, compound 2 dose-dependently increased the sub G1 cell population and arrested the G2-phase of the cell cycle, as revealed by flow cytometry. Mechanistically, compound 2 acts as an intracellular pro-oxidant by generating copious amounts of reactive oxygen species. Compound 2 also induced both loss of mitochondrial membrane potential (MMP) as well as lysosomal membrane permeabilization (LMP) in the MCF-7 cells. The impaired mitochondrial and lysosomal functions due to reactive oxygen species (ROS)-generation by compound 2 may contribute to its apoptotic property.
Keyphrases
- reactive oxygen species
- breast cancer cells
- cell cycle
- induced apoptosis
- flow cytometry
- cell cycle arrest
- cell death
- oxidative stress
- cell proliferation
- anti inflammatory
- signaling pathway
- endoplasmic reticulum stress
- stem cells
- bone marrow
- mass spectrometry
- climate change
- drug induced
- locally advanced
- induced pluripotent stem cells