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

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.

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

“…The C. zeylanicum component 2-methoxycinnamaldehyde downregulated NF-κB binding activity, proliferative control involving programmed cell death (Bax/Bcl-2 increase), and topoisomerases I/II activities, and upregulated lysosomal vacuolation in human lung adenocarcinoma A549 cells in vitro and in vivo [22]. In the same cancer line, similar anticancer effects (inhibition of proliferation and apoptosis induction) were shown after cuminaldehyde treatment [23]. Using hepatocellular carcinoma Hep 3B cells, Perng et al described proapoptotic and anti-inflammatory activities of 2-methoxycinnamaldehyde by inducing the mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, and DNA content increase in sub G1 phase and downregulation of NF-κB, cyclooxygenase-2 and prostaglandin E2 levels in vitro and in vivo [24].…”

A Narrative Review of the Antitumor Activity of Monoterpenes from Essential Oils: An Update

“…Cuminaldehyde has been shown to possess the ability to inhibit topoisomerase I and II activities and to upregulate lysosomal vacuolation on different cancer cells, exercising antitumor activity both in vitro and in vivo [ 93 , 94 ]. Using COLO 205 colorectal adenocarcinoma cells, Cherng's group found an IC50 of 16.31 μ M and a tumor growth inhibition of 69.4% in subcutaneous tumors with a dose of 20 mg/kg.…”

Prospects for Searching Multitarget Topoisomerase Inhibitors With Antitumor Properties

“…Одновременно он ингибировал активность Тор1, Тор2 и теломеразы в клетках аденокарциномы лёгкого A549, плоскоклеточного рака лёгкого NCI-H520 и аденокарциномы толстой кишки человека COLO205. Кроме того, куминальдегид был эффективен in vivo на ксенографтах опухолей человека, что позволило охарактеризовать его как ингибитор топоизомераз с противоопухолевым действием [43].…”