Antiproliferative effect of a novel synthesized carbazole compound on A549 lung cancer cell line.
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Date
2014
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Abstract
Increased death rates due to lung cancer have necessitated the search for
potential novel anticancer compounds such as carbazole derivatives.
Carbazoles are aromatic heterocyclic compounds with anticancer,
antibacterial and anti-inflammatory activity. The study investigated the ability
of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino]
pent-3-en-2-one (ECAP) to inhibit the proliferation of lung cancer cells and its
mechanism of action. ECAP was synthesized as a yellow powder with melting
point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium
bromide (MTT), lipid peroxidation and comet assays were used to assess the
anti-proliferative effects of the compound on A549 lung cancer cell line.
Protein expression was determined using western blots, apoptosis was
measured by luminometry for caspase-3/7, -8 and -9 and flow cytometry was
used to measure phosphatidylserine externalisation.
ECAP induced a p53 mediated apoptosis of lung cancer cells by significantly
down-regulating the expression of antioxidant defense proteins, Hsp70
(p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen
species (ROS) production. This resulted in DNA damage (p < 0.0001) and
subsequent up-regulation of Bax and caspase activity consequently inducing
apoptosis of lung cancer cells. These results demonstrate the potential
anticancer effects of ECAP on cultured lung cancer cells. However, further
investigation and characterization is required to fully understand the possible
use of carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-
en-2-one as potential lung cancer treatment.
Description
M. Med. Sc. University of KwaZulu-Natal, Durban 2014.
Keywords
Lungs--Cancer., Antibody-dependent cell cytotoxicity., Genetic toxicology., Proliferative vitreoretinopathy., Theses--Medical biochemistry., Theses--Chemical pathology.