New O-alkyl Chalcone Derivative Exhibits Antiproliferative Potential in Colorectal and Cervical Cancer Cells by Inducing G0/G1 Cell Cycle Arrest and Mitochondrial-mediated Apoptosis
Objective:
The main objective of the study was to investigate potential anticancer
activity in vitro of newly synthesized O-alkyl chalcone derivative (E)-1-(3-metoxy-
4-propoxyphenyl)-5-methylhex-1-en-3-on, (Chalcone 5) on cervical HeLa, colorectal
HCT-116 carcinoma cells and healthy MRC-5 cells.
Methods:
Using the MTT assay, the cytotoxic effect of Chalcone 5 and reference substances
dehydrozingerone and cisplatin were assessed. Using flow cytometry analysis,
the labeling process with Annexin V-FITC/7-AAD was carried out to assess the type of
cell death, while labeling with PI was used to examine the cell cycle progression in Chalcone
5 treated HeLa and HCT-116 cells. JC-10 probe was used to observe changes in
the mitochondrial membrane potential after Chalcone 5 therapy. The expression and cellular
localization of the important apoptotic proteins Bcl-2, Bax, caspase 3, and cytochrome
c were investigated using flow cytometry and immunofluorescence techniques.
Results:
The treatment of HeLa and HCT-116 cells with Chalcone 5 selectively induced
cytotoxicity, and apoptosis and increased the expression of active Bax and caspase-3
while decreasing the expression of Bcl-2, compared to healthy MRC5 cells. Furthermore,
Chalcone 5 decreased mitochondrial membrane potential and caused the release
of cytochrome c from mitochondria, thereby triggering the mitochondrial inner apoptotic
pathway. Moreover, Chalcone 5 arrested cell cycle progression in the G0/G1 phase in
both HeLa and HCT-116 cells.
Conclusion:
According to the study's findings, Chalcone 5 is a potentially useful candidate
drug for additional in vivo research on its anticancer properties against cervical and
colon cancer.
