Dihydrochalcone Derivative Induces Breast Cancer Cell Apoptosis via Intrinsic, Extrinsic, and ER Stress Pathways but Abolishes EGFRMAPK Pathway
Joint Authors
Rachakhom, Wasitta
Khaw-on, Patompong
Pompimon, Wilart
Banjerdpongchai, Ratana
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-18, 18 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-10-22
Country of Publication
Egypt
No. of Pages
18
Main Subjects
Abstract EN
Dihydrochalcone derivatives are active compounds that have been purified from the Thai medicinal plant Cyathostemma argenteum.
The objectives of this study were to investigate the effects of two dihydrochalcone derivatives on human breast cancer MDA-MB-231 and MCF-7 cell proliferation and to study the relevant mechanisms involved.
The two dihydrochalcone derivatives are 4′,6′-dihydroxy-2′,4-dimethoxy-5′-(2″-hydroxybenzyl)dihydrochalcone (compound 1) and calomelanone (2′,6′-dihydroxy-4,4′-dimethoxydihydrochalcone, compound 2), both of which induced cytotoxicity toward both cell lines in a dose-dependent manner by using MTT assay.
Treatment with both derivatives induced apoptosis as determined by annexin V-FITC/propidium iodide employing flow cytometry.
The reduction of mitochondrial transmembrane potential (staining with 3,3′-dihexyloxacarbocyanine iodide, DiOC6, employing a flow cytometer) was established in the compound 1-treated cells.
Compound 1 induced caspase-3, caspase-8, and caspase-9 activities in both cell lines, as has been determined by specific colorimetric substrates and a spectrophotometric microplate reader which indicated the involvement of both the extrinsic and intrinsic pathways.
Calcium ion levels in mitochondrial and cytosolic compartments increased in compound 1-treated cells as detected by Rhod-2AM and Fluo-3AM intensity, respectively, indicating the involvement of the endoplasmic reticulum (ER) stress pathway.
Compound 1 induced cell cycle arrest via enhanced atm and atr expressions and by upregulating proapoptotic proteins, namely, Bim, Bad, and tBid.
Moreover, compound 1 significantly inhibited the EGFR/MAPK signaling pathway.
In conclusion, compound 1 induced MDA-MB-231 and MCF-7 cell apoptosis via intrinsic, extrinsic, and ER stress pathways, whereas it ameliorated the EGFR/MAPK pathway in the MCF-7 cell line.
Consequently, it is believed that compound 1 could be effectively developed for cancer treatments.
American Psychological Association (APA)
Rachakhom, Wasitta& Khaw-on, Patompong& Pompimon, Wilart& Banjerdpongchai, Ratana. 2019. Dihydrochalcone Derivative Induces Breast Cancer Cell Apoptosis via Intrinsic, Extrinsic, and ER Stress Pathways but Abolishes EGFRMAPK Pathway. BioMed Research International،Vol. 2019, no. 2019, pp.1-18.
https://search.emarefa.net/detail/BIM-1127213
Modern Language Association (MLA)
Rachakhom, Wasitta…[et al.]. Dihydrochalcone Derivative Induces Breast Cancer Cell Apoptosis via Intrinsic, Extrinsic, and ER Stress Pathways but Abolishes EGFRMAPK Pathway. BioMed Research International No. 2019 (2019), pp.1-18.
https://search.emarefa.net/detail/BIM-1127213
American Medical Association (AMA)
Rachakhom, Wasitta& Khaw-on, Patompong& Pompimon, Wilart& Banjerdpongchai, Ratana. Dihydrochalcone Derivative Induces Breast Cancer Cell Apoptosis via Intrinsic, Extrinsic, and ER Stress Pathways but Abolishes EGFRMAPK Pathway. BioMed Research International. 2019. Vol. 2019, no. 2019, pp.1-18.
https://search.emarefa.net/detail/BIM-1127213
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1127213