Title:Discovery of a Novel Anti-Cancer Agent Targeting Both Topoisomerase I & II as Well as Telomerase Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo: Cinnamomum verum Component Cuminaldehyde
Volume: 16
Issue: 9
Author(s): Ta-Wei Chen, Kuen-daw Tsai, Shu-mei Yang, Ho-Yiu Wong, Yi-Heng Liu, Jonathan Cherng, Kuo-Shen Chou, Yang-Tz Wang, Janise Cuizon and Jaw-Ming Cherng
Affiliation:
Keywords:
A549 cells, anticancer, cuminaldehyde, lysosomal vacuolation, telomerase, topoisomerase I, topoisomerase II,
xenograft.
Abstract: Cinnamomum verum is used to make the spice cinnamon and has been
used for more than 5000 years by both of the two most ancient forms of medicine
in the words: Ayurveda and traditional Chinese herbal medicines for various
applications such as adenopathy, rheumatism, dermatosis, dyspepsia, stroke,
tumors, elephantiasis, trichomonas, yeast, and virus infections. We evaluated the
anticancer effect of cuminaldehyde (CuA), a constituent of the bark of the plant,
and its underlying molecular biomarkers associated with carcinogenesis in human
lung adenocarcinoma A549 cells. The results show that cuminaldehyde suppressed
proliferation and induced apoptosis as indicated by mitochondrial membrane
potential loss, activation of caspase 3 and 9, increase in annexin V+PI+ cells, and
morphological characteristics of apoptosis, including blebbing of plasma membrane, nuclear
condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and
moment. In addition, cuminaldehyde also induced lysosomal vacuolation with increased volume of
acidic compartments (VAC), suppressions of both topoisomerase I & II as well as telomerase
activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of
cuminaldehyde was also evident in a nude mice model. Taken together, the data suggest that the
growth-inhibitory effect of cuminaldehyde against A549 cells is accompanied by downregulations of
proliferative control involving apoptosis, both topoisomerase I & II as well as telomerase activities,
together with an upregulation of lysosomal vacuolation and VAC. Similar effects (including all of the
above-mentioned effects) were found in other cell lines, including human lung squamous cell
carcinoma NCI-H520 and colorectal adenocarcinoma COLO 205 (results not shown). Our data
suggest that cuminaldehyde could be a potential agent for anticancer therapy.
