一种目标为拓扑异构酶I & II的新抗肿瘤制剂和在体外和在体内的人肺腺癌A549细胞端粒酶活性：肉桂八角成分枯茗醛的发现

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 and Janise Cuizon, Jaw-Ming Cherng

Affiliation:

关键词: A549细胞，抗癌，枯茗醛，溶酶体空泡化，端粒酶，拓扑异构酶I，拓扑异构酶II，异种移植

摘要: 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.

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Ta-Wei Chen, Kuen-daw Tsai, Shu-mei Yang, Ho-Yiu Wong, Yi-Heng Liu, Jonathan Cherng, Kuo-Shen Chou, Yang-Tz Wang and Janise Cuizon, Jaw-Ming Cherng , 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, Current Cancer Drug Targets 2016; 16 (9) . https://dx.doi.org/10.2174/1568009616666160426125526