Inhibitory effects of Cinnamomum burmannii Blume stem bark extract and trans-cinnamaldehyde on nasopharyngeal carcinoma cells; synergism with cisplatin

Daker,Maelinda; Lin,Voon  Yee; Akowuah,Gabriel  Akyirem; Yam,Mun  Fei; Ahmad,Mariam

doi:10.3892/etm.2013.1041

Inhibitory effects of Cinnamomum burmannii Blume stem bark extract and trans-cinnamaldehyde on nasopharyngeal carcinoma cells; synergism with cisplatin

Authors:
- Maelinda Daker
- Voon Yee Lin
- Gabriel Akyirem Akowuah
- Mun Fei Yam
- Mariam Ahmad
View Affiliations

Affiliations: Molecular Pathology Unit, Institute for Medical Research, Jalan Pahang, Kuala Lumpur 50588, Malaysia, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia, Faculty of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia
Published online on: April 2, 2013 https://doi.org/10.3892/etm.2013.1041
Pages: 1701-1709

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Nasopharyngeal carcinoma (NPC) is a malignancy that occurs in the epithelium of the nasopharynx. The standard treatment of NPC patients with locoregionally advanced stages is problematic and is often associated with toxicities. Therefore, it is essential to screen for naturally occurring compounds with strong apoptosis-inducing activity and minimal toxicity. This study investigated the effects of the standardized methanol extract of Cinnamomum burmannii Blume stem bark and its main constituent, trans-cinnamaldehyde (TCA), on human NPC cell lines. The content of TCA in C. burmannii methanol extract was standardized to be 13.61% w/w by means of gas chromatography-mass spectrometry (GC-MS). NPC cell proliferation was clearly inhibited within 24 h of treatment, with TCA exhibiting greater activity than the methanol extract. TCA was more active against NPC cells compared with cisplatin. There was a pronounced downregulation of the proliferation markers, Ki67 and proliferating cell nuclear antigen (PCNA) in the TCA-treated cells; while morphological observation indicated the induction of apoptosis. Caspase activation and prominent DNA damage, which are markers of apoptosis induction were detected. TCA demonstrated the ability to scavenge nitric oxide. The simultaneous combination of TCA and cisplatin produced synergistic anti-proliferative effects. Collectively, these data indicate the potential use of TCA for the treatment of NPC.

View Figures

View References

1.	Wei WI and Sham JS: Nasopharyngeal carcinoma. Lancet. 365:2041–2054. 2005. View Article : Google Scholar : PubMed/NCBI
2.	Tao Q and Chan AT: Nasopharyngeal carcinoma: molecular pathogenesis and therapeutic developments. Expert Rev Mol Med. 9:1–24. 2007.PubMed/NCBI
3.	van Leeuwen IMM and Laín S: Pharmacological manipulation of the cell cycle and metabolism to protect normal tissues against conventional anticancer drugs. Oncotarget. 2:274–276. 2011.PubMed/NCBI
4.	Cao H, Graves D and Anderson R: Cinnamon extract regulates glucose transporter and insulin-signaling gene expression in mouse adipocytes. Phytomed. 17:1027–1032. 2010. View Article : Google Scholar : PubMed/NCBI
5.	Bandar E: Pharmaceutical applications and phytochemical profile of Cinnamomum burmannii. Pharmacog Rev. 6:125–131. 2012. View Article : Google Scholar : PubMed/NCBI
6.	Lv G, Huang W, Yang F, Li J and Li S: Pressurized liquid extraction and GC-MS analysis for simulateneous determination of seven components in Cinnamomum cassia and effect of sample preparation. J Sep Sci. 33:2341–2348. 2010. View Article : Google Scholar : PubMed/NCBI
7.	Gomez-Flores R, Hernández-Martínez H, Tamez-Guerra P, et al: Antitumor and immunomodulating potential of Coriandrum sativum, Piper nigrum and Cinnamomum zeylanicum. J Nat Prod. 3:54–63. 2010.
8.	Koppikar S, Choudhari A, Suryavanshi S, Kurnari S, Chattopadhyay S and Kaul-Ghanekar R: Aqueous cinnamon extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential. BMC Cancer. 10:2102010.PubMed/NCBI
9.	Kwon HK, Hwang JS, So JS, et al: Cinnamon extract induces tumor cell death through inhibition of NFκB and AP1. BMC Cancer. 10:3922010.PubMed/NCBI
10.	Wu S, Ng L and Lin C: Cinnamaldehyde-induced apoptosis in human PLC/PRF/5 cells through activation of the proapoptotic Bcl-2 family proteins and MAPK pathway. Life Sciences. 77:938–951. 2005. View Article : Google Scholar : PubMed/NCBI
11.	Cabello CM, Bair WB III, Lamore SD, et al: The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness and tumor growth. Free Radic Biol Med. 46:220–231. 2009. View Article : Google Scholar : PubMed/NCBI
12.	Zhang JH, Liu LQ, He YI, Kong WJ and Huang SA: Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells. Acta Pharmacologica Sinica. 31:861–866. 2010. View Article : Google Scholar : PubMed/NCBI
13.	Ng LT and Wu SJ: Antiproliferative activity of Cinnamomum cassia constituents and effects of pifithrin-alpha on their apoptotic signaling pathways in Hep G2 cells. Evid Based Complement Alternat Med. 2011:4921482011.
14.	Huang DP, Ho JH, Poon YF, et al: Establishment of a cell line (NPC/HK1) from a differentiated squamous carcinoma of the nasopharynx. Int J Cancer. 26:127–132. 1980. View Article : Google Scholar : PubMed/NCBI
15.	Cheung ST, Huang DP, Hui AB, et al: Nasopharyngeal carcinoma cell line (C666-1) consistently harbouring Epstein-Barr virus. Int J Cancer. 83:121–126. 1999. View Article : Google Scholar : PubMed/NCBI
16.	Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A and Fusenig NE: Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol. 106:761–771. 1988. View Article : Google Scholar : PubMed/NCBI
17.	Chou TC: Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 58:621–681. 2006. View Article : Google Scholar : PubMed/NCBI
18.	Rao M: Nitric oxide scavenging by curcuminoids. J Pharm Pharmacol. 49:105–107. 1997. View Article : Google Scholar
19.	Unlu M, Ergene E, Unlu G, Zeytinoglu H and Vural N: Composition, antimicrobial activity and in vitro cytotoxicity of essential oil from Cinnamomum zeylanicum Blume (Lauraceae). Food Chem Toxicol. 48:3274–3280. 2010. View Article : Google Scholar : PubMed/NCBI
20.	Dickey J, Redon C, Nakamura A, Baird B, Sedelnikova O and Bonner W: H2AX: functional roles and potential applications. Chromosomes. 118:683–692. 2009. View Article : Google Scholar : PubMed/NCBI
21.	Kuo L and Yang L: Gamma-H2AX - a novel biomarker for DNA double-strand breaks. In Vivo. 22:305–309. 2008.PubMed/NCBI
22.	Ayoub N, Jeyasekharan A, Bernal J and Venkitaraman A: Paving the way for H2AX phosphorylation: chromatin changes in the DNA damage response. Cell Cycle. 8:1494–1500. 2009. View Article : Google Scholar : PubMed/NCBI
23.	Chung W, Seung H, Jae W, et al: 2-Hydroxycinnamaldehyde inhibits SW620 colon cancer cell growth through AP-1 inactivation. J Pharmacol Sci. 104:19–28. 2007. View Article : Google Scholar : PubMed/NCBI
24.	Daker M, Ahmad M and Khoo ASB: Quercetin-induced inhibition and synergistic activity with cisplatin - a chemotherapeutic strategy for nasopharyngeal carcinoma cells. Cancer Cell Int. 12:342012. View Article : Google Scholar : PubMed/NCBI
25.	Seung H, Sun Y, Dong J, et al: Inhibitory effect of 2-hydroxycinnamaldehyde on nitric oxide production through inhibition of NFκB activation in RAW 264.7 cells. Biochem Pharmacol. 69:791–799. 2005.
26.	Jagetia S, Balgia M and Babu K: Evaluation of nitric oxide scavenging activity of certain herbal formulation in vitro. Phytother Res. 18:561–565. 2004. View Article : Google Scholar : PubMed/NCBI
27.	Korkmaz B, Buharalioglu K, Sahan-Firat S, Cuez T, Demiryurek T and Tunctan B: Activation of MEK1/ERK1/2/iNOS/sGC/PKG pathway associated with peroxynitrite formation contributes to hypotension and vascular hyporeactivity in endotoxemic rats. Nitric Oxide. 24:160–172. 2011. View Article : Google Scholar : PubMed/NCBI