Cinnamomum verumComponent 2-Methoxycinnamaldehyde: A Novel Anticancer Agent with Both Anti-Topoisomerase I and II Activities in Human Lung Adenocarcinoma A549 CellsIn VitroandIn Vivo

Wong, Ho-Yiu; Tsai, Kuen-Daw; Liu, Yiheng; Yang, Shumei; Chen, Ta-Wei; Cherng, Jonathan; Chou, Kuo-Shen; Chang, Chen-Mei; Yao, Belen T.; Cherng, Jaw-Ming

doi:10.1002/ptr.5536

Cited by 29 publications

(8 citation statements)

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“…In another preclinical study, cinnamaldehyde has been documented as an antioxidant that reduced visfatin-induced breast cancer progression in vitro and in vivo [21]. 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].…”

Section: Introductionmentioning

confidence: 98%

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

et al. 2020

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Comprehensive oncology research suggests an important role of phytochemicals or whole plant foods in the modulation of signaling pathways associated with anticancer action. The goal of this study is to assess the anticancer activities of Cinnamomum zeylanicum L. using rat, mouse, and cell line breast carcinoma models. C. zeylanicum (as bark powder) was administered in the diet at two concentrations of 0.1% (w/w) and 1% (w/w) during the whole experiment in chemically induced rat mammary carcinomas and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular evaluations of mammary gland tumors in rodents were carried out. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were performed. The dominant metabolites present in the tested C. zeylanicum essential oil (with relative content over 1%) were cinnamaldehyde, cinnamaldehyde dimethyl acetal, cinnamyl acetate, eugenol, linalool, eucalyptol, limonene, o-cymol, and α-terpineol. The natural mixture of mentioned molecules demonstrated significant anticancer effects in our study. In the mouse model, C. zeylanicum at a higher dose (1%) significantly decreased tumor volume by 44% when compared to controls. In addition, treated tumors showed a significant dose-dependent decrease in mitotic activity index by 29% (0.1%) and 45.5% (1%) in comparison with the control group. In rats, C. zeylanicum in both doses significantly reduced the tumor incidence by 15.5% and non-significantly suppressed tumor frequency by more than 30% when compared to controls. An evaluation of the mechanism of anticancer action using valid oncological markers showed several positive changes after treatment with C. zeylanicum. Histopathological analysis of treated rat tumor specimens showed a significant decrease in the ratio of high-/low-grade carcinomas compared to controls. In treated rat carcinomas, we found caspase-3 and Bax expression increase. On the other hand, we observed a decrease in Bcl-2, Ki67, VEGF, and CD24 expressions and MDA levels. Assessment of epigenetic changes in rat tumor cells in vivo showed a significant decrease in lysine methylation status of H3K4m3 and H3K9m3 in the high-dose treated group, a dose-dependent increase in H4K16ac levels (H4K20m3 was not changed), down-regulations of miR21 and miR155 in low-dose cinnamon groups (miR22 and miR34a were not modulated), and significant reduction of the methylation status of two out of five gene promoters—ATM and TIMP3 (PITX2, RASSF1, PTEN promoters were not changed). In vitro study confirmed results of animal studies, in that the essential oil of C. zeylanicum displayed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using MTS, BrdU, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). As a conclusion, C. zeylanicum L. showed chemopreventive and therapeutic activities in animal breast carcinoma models that were also significantly confirmed by mechanistic evaluations in vitro and in vivo.

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Section: Introductionmentioning

confidence: 98%

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

et al. 2020

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“…Cinnamon is native to Sri Lanka and southern India. It has many uses in food, medicine, pharmaceutical, and cosmetics industries (Han & Parker, 2017;Madhavadas & Subramanian, 2017;Mesripour, Moghimi, & Rafieian-Kopaie, 2016;Nayak, Chinta, & Jetti, 2017;Tulini et al, 2017;Wong et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of cinnamon bark extract against ischemia–reperfusion injury and arrhythmias in rat

Sedighi

Nazari

Faghihi

et al. 2018

Phytotherapy Research

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Cinnamomum zeylanicum (cinnamon) is a plant with potent antioxidant activity and has been used in traditional medicine for improvement of heart function. The effects of cinnamon bark ethanolic extract were investigated against ischemia-induced arrhythmias and heart injury in an in vivo rat model of regional heart ischemia. The extract was also standardized, and its antioxidant activity was evaluated. Adult male Sprague-Dawley rats were subjected to 30 min of ischemia by occlusion of the left anterior descending coronary artery followed by 5 days of reperfusion. Thirty-two animals were randomized to receive daily oral administration of vehicle or C. zeylanicum bark extract (intragastric, 50, 100, or 200 mg/kg) 14 days before ischemia. C. zeylanicum was standardized through HPLC analysis. Administration of cinnamon bark extract significantly improved ischemia/reperfusion-induced myocardial injury as evidenced by reduction of the infarct size. Also, during the ischemic period, ventricular tachycardia and ventricular ectopic beats episodes decreased as compared with that of the control group. The extract stabilized the ST segment changes and QTc shortening, decreased R-wave amplitude, and increased heart rate during ischemia. The extract also caused significant elevations in serum superoxide dismutase and glutation proxidase activities as well as a significant decrease in serum cardiac troponin I, lactate dehydrogenase, and malondialdehyde levels, 5 days after reperfusion. In HPLC analysis, the amounts of Cinamic acid, Methyl eugenol, and Cinnamaldehyde were 8.99 ± 0.5, 13.02 ± 1.8, and 14.63 ± 1.1 mg/g, respectively. The results show that the ethanolic extract of cinnamon bark is able to protect the heart against ischemia-reperfusion injury probably due to its antioxidant properties. Hence, it might be beneficial in these patients and this remedy might be used for preparation of new drugs.

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“…Recently, anti‐inflammation activity of 4‐MCA has been recognized (Srisook et al, ). Although anticancer effect of several cinnamaldehyde derivatives have been noticed (Han et al, ; Jeong et al, ; Lin, Wu, & Lin, ; Perng et al, ; Wong et al, ), this is the first report on in vitro antitumor activity of 4‐MCA.…”

Section: Resultsmentioning

confidence: 80%

Cytotoxic effects of Etlingera pavieana rhizome on various cancer cells and identification of a potential anti-tumor component

et al. 2018

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Much effort over the last several decades has been made to identify new anticancer agents, preferably with reduced adverse side effects. In this study, cytotoxic activity of rhizome extract from Etlingera pavieana (Pierre ex Gagnep.) R.M.Sm. was assessed. We demonstrate that ethanolic extract (EE) of E. pavieana rhizome shows reduced viabilities of several cancer cell lines in doseand time-dependent manners. Following cytotoxic-guided isolation of EE, the bioactive compound trans-4-methoxycinnamaldehyde (4-MCA) was identified. 4-MCA exhibited a dose-dependent inhibitory effect on cancer cell growth with the IC 50 values ranging from 34 to 40 mM, which are approximately four times lower than that of noncancerous cells. This antiproliferative effect might be due to its cooperative actions of inducing apoptosis and arresting cell cycle at G2/M phase. To the best of our knowledge, this is the first report on the in vitro antitumor promoting activity of 4-MCA. Practical applications Rhizome of E. pavieana (Zingiberaceae) has been widely used as spices and a medicinal plant in Thailand, Cambodia, Laos, and Vietnam. In this study, we demonstrated the medicinal role of this plant on suppressing the growth of various cancer cells of common cancer types including those of breast, cervix, liver, and colon/rectum. Moreover, we verified that this action was, at least in part, due to one of its constituents, 4-MCA. Overall results demonstrated the potential cytotoxic activities of 4-MCA toward cancer cells, including inhibition of cell proliferation and colony formation, induction of apoptosis, and cell cycle arrest whereas it exhibited negligible effect on noncancerous cells. The comprehensive characterization of E. pavieana rhizome performed in this study, highlights the pharmaceutical potential of 4-MCA, one of its major constituents, to be a promising candidate for future development of new cancer regimen. K E Y W O R D S apoptosis induction, cell cycle arrest, cytotoxicity, Etlingera pavieana, 4-methoxycinnamaldehyde

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Cinnamomum verumComponent 2-Methoxycinnamaldehyde: A Novel Anticancer Agent with Both Anti-Topoisomerase I and II Activities in Human Lung Adenocarcinoma A549 CellsIn VitroandIn Vivo

Cited by 29 publications

References 49 publications

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

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

Protective effects of cinnamon bark extract against ischemia–reperfusion injury and arrhythmias in rat

Cytotoxic effects of Etlingera pavieana rhizome on various cancer cells and identification of a potential anti-tumor component

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