Chalcones with electron-withdrawing and electron-donating substituents: anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis and regulation of apoptotic proteins

Chun Wai Mai; Marzieh Yaeghoobi; Noorsaadah Abd-Rahman; Yew Beng Kang; Mallikarjuna Rao Pichika

doi:10.1016/j.ejmech.2014.03.002

Chalcones with electron-withdrawing and electron-donating substituents: anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis and regulation of apoptotic proteins

Eur J Med Chem. 2014 Apr 22:77:378-87. doi: 10.1016/j.ejmech.2014.03.002. Epub 2014 Mar 3.

Authors

Chun Wai Mai¹, Marzieh Yaeghoobi², Noorsaadah Abd-Rahman², Yew Beng Kang¹, Mallikarjuna Rao Pichika³

Affiliations

¹ Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
² Drug Design and Development Research Group, Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia.
³ Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. Electronic address: mallikarjunarao_pichika@imu.edu.my.

PMID: 24675137
DOI: 10.1016/j.ejmech.2014.03.002

Abstract

In the present study, a series of 46 chalcones were synthesised and evaluated for antiproliferative activities against the human TRAIL-resistant breast (MCF-7, MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29), nasopharyngeal (CNE-1), erythromyeloblastoid (K-562) and T-lymphoblastoid (CEM-SS) cancer cells. The chalcone 38 containing an amino (-NH2) group on ring A was the most potent and selective against cancer cells. The effects of the chalcone 38 on regulation of 43 apoptosis-related markers in HT-29 cells were determined. The results showed that 20 apoptotic markers (Bad, Bax, Bcl-2, Bcl-w, Bid, Bim, CD40, Fas, HSP27, IGF-1, IGFBP-4, IGFBP-5, Livin, p21, Survivin, sTNF-R2, TRAIL-R2, XIAP, caspase-3 and caspase-8) were either up regulated or down regulated.

Keywords: Anti-proliferative; Apoptosis proteins; Chalcones; Human colorectal cancer (HT-29) cells; TRAIL-resistant tumours.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Biomarkers, Tumor / metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Chalcones / chemical synthesis
Chalcones / chemistry*
Chalcones / pharmacology*
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm / drug effects*
Drug Screening Assays, Antitumor
Electrons*
HT29 Cells
HeLa Cells
Hep G2 Cells
Humans
MCF-7 Cells
Molecular Structure
Structure-Activity Relationship
TNF-Related Apoptosis-Inducing Ligand / pharmacology*

Substances

Antineoplastic Agents
Biomarkers, Tumor
Chalcones
TNF-Related Apoptosis-Inducing Ligand