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Research Article

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

Author(s):

Ivana Nikolic, Jovan Luković, Tijana Marković, Tijana Ristić, Marija Bulić, Marija Anđelković*, Marija Šorak, Milica Milinković, Jovana Muškinja, Petar Čanović and Marina Mitrović   Pages 1 - 19 ( 19 )

Abstract:


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.

Keywords:

Apoptosis, colon cancer, chalcones, cervical cancer, cell death, caspase-3, bax.

Affiliation:



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