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.
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.
Ta-Wei
TW
Chen
Kuen-Daw
KD
Tsai
Shu-Mei
SM
Yang
Ho-Yiu
HY
Wong
Yi-Heng
YH
Liu
Jonathan
J
Cherng
Kuo-Shen
KS
Chou
Yang-Tz
YT
Wang
Janise
J
Cuizon
Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan 26546, Taiwan, ROC. happy.professor@yahoo.com.
Jaw-Ming
JM
Cherng
D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001547:Benzaldehydes / Q000494:pharmacology*; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D000081007:Cymenes; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy / Q000379:methods; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D001547:Benzaldehydes; D000081007:Cymenes; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D019098:Telomerase; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; C007165:cuminaldehyde