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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2016 | Research article

Antiproliferation of Cryptocarya concinna-derived cryptocaryone against oral cancer cells involving apoptosis, oxidative stress, and DNA damage

Authors: Hsun-Shuo Chang, Jen-Yang Tang, Ching-Yu Yen, Hurng-Wern Huang, Chang-Yi Wu, Yi-An Chung, Hui-Ru Wang, Ih-Sheng Chen, Ming-Yii Huang, Hsueh-Wei Chang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

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Abstract

Background

Cryptocarya-derived crude extracts and their compounds have been reported to have an antiproliferation effect on several types of cancers but their impact on oral cancer is less well understood.

Methods

We examined the cell proliferation effect and mechanism of C. concinna-derived cryptocaryone (CPC) on oral cancer cells in terms of cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial depolarization, and DNA damage.

Results

We found that CPC dose-responsively reduced cell viability of two types of oral cancer cells (Ca9-22 and CAL 27) in MTS assay. The CPC-induced dose-responsive apoptosis effects on Ca9-22 cells were confirmed by flow cytometry-based sub-G1 accumulation, annexin V staining, and pancaspase analyses. For oral cancer Ca9-22 cells, CPC also induced oxidative stress responses in terms of ROS generation and mitochondrial depolarization. Moreover, γH2AX flow cytometry showed DNA damage in CPC-treated Ca9-22 cells. CPC-induced cell responses in terms of cell viability, apoptosis, oxidative stress, and DNA damage were rescued by N-acetylcysteine pretreatment, suggesting that oxidative stress plays an important role in CPC-induced death of oral cancer cells.

Conclusions

CPC is a potential ROS-mediated natural product for anti-oral cancer therapy.
Appendix
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Literature
1.
Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4–5):309–16.CrossRefPubMed
2.
Petersen PE. Oral cancer prevention and control--the approach of the World Health Organization. Oral Oncol. 2009;45(4-5):454–60.CrossRefPubMed
3.
Myoung H, Hong SP, Yun PY, Lee JH, Kim MJ. Anti-cancer effect of genistein in oral squamous cell carcinoma with respect to angiogenesis and in vitro invasion. Cancer Sci. 2003;94(2):215–20.CrossRefPubMed
4.
Yen CY, Chen CH, Chang CH, Tseng HF, Liu SY, Chuang LY, Wen CH, Chang HW. Matrix metalloproteinases (MMP) 1 and MMP10 but not MMP12 are potential oral cancer markers. Biomarkers. 2009;14(4):244–9.CrossRefPubMed
5.
Yen CY, Huang CY, Hou MF, Yang YH, Chang CH, Huang HW, Chen CH, Chang HW. Evaluating the performance of fibronectin 1 (FN1), integrin alpha4beta1 (ITGA4), syndecan-2 (SDC2), and glycoprotein CD44 as the potential biomarkers of oral squamous cell carcinoma (OSCC). Biomarkers. 2013;18(1):63–72.CrossRefPubMed
6.
Davies-Coleman MT, Rivett DEA. Naturally occurring 6-substituted 5,6-dihydro-α-pyrones. Prog Chem Org Nat Prod. 1989;55:1–35.
7.
Ong CY, Ling SK, Ali RM, Chee CF, Samah ZA, Ho AS, Teo SH, Lee HB. Systematic analysis of in vitro photo-cytotoxic activity in extracts from terrestrial plants in Peninsula Malaysia for photodynamic therapy. J Photochem Photobiol B. 2009;96(3):216–22.CrossRefPubMed
8.
Huang HW, Chung YA, Chang HS, Tang JY, Chen IS, Chang HW. Antiproliferative effects of methanolic extracts of Cryptocarya concinna Hance roots on oral cancer Ca9-22 and CAL 27 cell lines involving apoptosis, ROS induction, and mitochondrial depolarization. ScientificWorldJournal. 2014;2014:180462.PubMedPubMedCentral
9.
Dumontet V, Van Hung N, Adeline MT, Riche C, Chiaroni A, Sevenet T, Gueritte F. Cytotoxic flavonoids and alpha-pyrones from Cryptocarya obovata. J Nat Prod. 2004;67(5):858–62.CrossRefPubMed
10.
Allard PM, Dau ET, Eydoux C, Guillemot JC, Dumontet V, Poullain C, Canard B, Gueritte F, Litaudon M. Alkylated flavanones from the bark of Cryptocarya chartacea as dengue virus NS5 polymerase inhibitors. J Nat Prod. 2011;74(11):2446–53.CrossRefPubMed
11.
Wu TS, Sun CR, Lee KH. Cytotoxic and anti-HIV phenanthroindolizidine alkaloids from Cryptocarya chinensis. Nat Prod Commun. 2012;7(6):725–7.PubMedPubMedCentral
12.
Chou TH, Chen JJ, Peng CF, Cheng MJ, Chen IS. New flavanones from the leaves of Cryptocarya chinensis and their antituberculosis activity. Chem Biodivers. 2011;8(11):2015–24.CrossRefPubMed
13.
Nasrullah AA, Zahari A, Mohamad J, Awang K. Antiplasmodial alkaloids from the bark of Cryptocarya nigra (Lauraceae). Molecules. 2013;18(7):8009–17.CrossRefPubMed
14.
Davis RA, Demirkiran O, Sykes ML, Avery VM, Suraweera L, Fechner GA, Quinn RJ. 7',8'-Dihydroobolactone, a typanocidal alpha-pyrone from the rainforest tree Cryptocarya obovata. Bioorg Med Chem Lett. 2010;20(14):4057–9.CrossRefPubMed
15.
Feng R, Guo ZK, Yan CM, Li EG, Tan RX, Ge HM. Anti-inflammatory flavonoids from Cryptocarya chingii. Phytochemistry. 2012;76:98–105.CrossRefPubMed
16.
Usman H, Hakim EH, Harlim T, Jalaluddin MN, Syah YM, Achmad SA, Takayama H. Cytotoxic chalcones and flavanones from the tree bark of Cryptocarya costata. Z Naturforsch C. 2006;61(3-4):184–8.CrossRefPubMed
17.
Kurniadewi F, Juliawaty LD, Syah YM, Achmad SA, Hakim EH, Koyama K, Kinoshita K, Takahashi K. Phenolic compounds from Cryptocarya konishii: their cytotoxic and tyrosine kinase inhibitory properties. J Nat Med. 2010;64(2):121–5.CrossRefPubMed
18.
Liao JC. Lauraceae in Flora of Taiwan, 2nd ed. Editorial Committee of the Flora of Taiwan; Taipei, Taiwan. 1996, 2:448-451.
19.
Chen YC, Kung FL, Tsai IL, Chou TH, Chen IS, Guh JH. Cryptocaryone, a natural dihydrochalcone, induces apoptosis in human androgen independent prostate cancer cells by death receptor clustering in lipid raft and nonraft compartments. J Urol. 2010;183(6):2409–18.CrossRefPubMed
20.
Leon-Gonzalez AJ, Lopez-Lazaro M, Espartero JL, Martin-Cordero C. Cytotoxic activity of dihydrochalcones isolated from Corema album leaves against HT-29 colon cancer cells. Nat Prod Commun. 2013;8(9):1255–6.PubMed
21.
Chiu CC, Haung JW, Chang FR, Huang KJ, Huang HM, Huang HW, Chou CK, Wu YC, Chang HW. Golden berry-derived 4beta-hydroxywithanolide E for selectively killing oral cancer cells by generating ROS, DNA damage, and apoptotic pathways. PLoS One. 2013;8(5):e64739.CrossRefPubMedPubMedCentral
22.
Jiang L, Ji N, Zhou Y, Li J, Liu X, Wang Z, Chen Q, Zeng X. CAL 27 is an oral adenosquamous carcinoma cell line. Oral Oncol. 2009;45(11):e204–207.CrossRefPubMed
23.
Chen BH, Chang HW, Huang HM, Chong IW, Chen JS, Chen CY, Wang HM. (-)-Anonaine induces DNA damage and inhibits growth and migration of human lung carcinoma h1299 cells. J Agric Food Chem. 2011;59(6):2284–90.CrossRefPubMed
24.
Chiu CC, Liu PL, Huang KJ, Wang HM, Chang KF, Chou CK, Chang FR, Chong IW, Fang K, Chen JS et al. Goniothalamin inhibits growth of human lung cancer cells through DNA damage, apoptosis, and reduced migration ability. J Agric Food Chem. 2011;59(8):4288–93.CrossRefPubMed
25.
Kaufmann SH, Lee SH, Meng XW, Loegering DA, Kottke TJ, Henzing AJ, Ruchaud S, Samejima K, Earnshaw WC. Apoptosis-associated caspase activation assays. Methods. 2008;44(3):262–72.CrossRefPubMed
26.
Yeh CC, Tseng CN, Yang JI, Huang HW, Fang Y, Tang JY, Chang FR, Chang HW. Antiproliferation and induction of apoptosis in Ca9-22 oral cancer cells by ethanolic extract of Gracilaria tenuistipitata. Molecules. 2012;17(9):10916–27.CrossRefPubMed
27.
Yeh CC, Yang JI, Lee JC, Tseng CN, Chan YC, Hseu YC, Tang JY, Chuang LY, Huang HW, Chang FR. Anti-proliferative effect of methanolic extract of Gracilaria tenuistipitata on oral cancer cells involves apoptosis, DNA damage, and oxidative stress. BMC Complement Altern Med. 2012;12(1):142.CrossRefPubMedPubMedCentral
28.
Yen CY, Chiu CC, Haung RW, Yeh CC, Huang KJ, Chang KF, Hseu YC, Chang FR, Chang HW, Wu YC. Antiproliferative effects of goniothalamin on Ca9-22 oral cancer cells through apoptosis, DNA damage and ROS induction. Mutat Res. 2012;747(2):253–8.CrossRefPubMed
29.
Yu FS, Yang JS, Yu CS, Lu CC, Chiang JH, Lin CW, Chung JG. Safrole induces apoptosis in human oral cancer HSC-3 cells. J Dent Res. 2011;90(2):168–74.CrossRefPubMed
30.
Yen CY, Hou MF, Yang ZW, Tang JY, Li KT, Huang HW, Huang YH, Lee SY, Fu TF, Hsieh CY et al. Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage. BMC Complement Altern Med. 2015;15(1):94.CrossRefPubMedPubMedCentral
31.
Chan WH, Shiao NH, Lu PZ. CdSe quantum dots induce apoptosis in human neuroblastoma cells via mitochondrial-dependent pathways and inhibition of survival signals. Toxicol Lett. 2006;167(3):191–200.CrossRefPubMed
32.
Shieh JM, Shen CJ, Chang WC, Cheng HC, Chan YY, Huang WC, Chang WC, Chen BK. An increase in reactive oxygen species by deregulation of ARNT enhances chemotherapeutic drug-induced cancer cell death. PLoS One. 2014;9(6):e99242.CrossRefPubMedPubMedCentral
33.
Lee WC, Li LC, Chen JB, Chang HW. Indoxyl sulfate-induced oxidative stress, mitochondrial dysfunction, and impaired biogenesis are partly protected by Vitamin C and N-acetylcysteine. ScientificWorldJournal. 2015;2015:620826.PubMedPubMedCentral
34.
Lin MH, Hsieh WF, Chiang WF, Hong WZ, Hsu YR, Cheng YC, Chen TC, Hsu KC, Lin PY, Liu SY. Autophagy induction by the 30-100 kDa fraction of areca nut in both normal and malignant cells through reactive oxygen species. Oral Oncol. 2010;46(11):822–8.CrossRefPubMed
35.
Yen CY, Lin MH, Liu SY, Chiang WF, Hsieh WF, Cheng YC, Hsu KC, Liu YC. Arecoline-mediated inhibition of AMP-activated protein kinase through reactive oxygen species is required for apoptosis induction. Oral Oncol. 2011;47(5):345–51.CrossRefPubMed
36.
Han MH, Park C, Jin CY, Kim GY, Chang YC, Moon SK, Kim WJ, Choi YH. Apoptosis induction of human bladder cancer cells by sanguinarine through reactive oxygen species-mediated up-regulation of early growth response gene-1. PLoS One. 2013;8(5):e63425.CrossRefPubMedPubMedCentral
37.
Raj L, Ide T, Gurkar AU, Foley M, Schenone M, Li X, Tolliday NJ, Golub TR, Carr SA, Shamji AF et al. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature. 2011;475(7355):231–4.CrossRefPubMedPubMedCentral
38.
Ding H, Han C, Guo D, Chin YW, Ding Y, Kinghorn AD, D'Ambrosio SM. Selective induction of apoptosis of human oral cancer cell lines by avocado extracts via a ROS-mediated mechanism. Nutr Cancer. 2009;61(3):348–56.
39.
Dumontet V, Gaspard C, Hung NV, Fahy J, Tchertanov L, Se’venet T, Gue´ritte F. New cytotoxic flavonoids from Cryptocarya infectoria. Tetrahedron. 2001;57:6189–96.
40.
41.
Yen YH, Farooqi AA, Li KT, Butt G, Tang JY, Wu CY, Cheng YB, Hou MF, Chang HW. Methanolic extracts of Solieria robusta inhibits proliferation of oral cancer Ca9-22 cells via apoptosis and oxidative stress. Molecules. 2014;19(11):18721–32.CrossRefPubMed
42.
Belka C, Budach W. Anti-apoptotic Bcl-2 proteins: structure, function and relevance for radiation biology. Int J Radiat Biol. 2002;78(8):643–58.CrossRefPubMed
43.
Chen JJ, Lee HH, Duh CY, Chen IS. Cytotoxic chalcones and flavonoids from the leaves of Muntingia calabura. Planta Med. 2005;71(10):970–3.CrossRefPubMed
44.
Farooqi AA, Fayyaz S, Hou MF, Li KT, Tang JY, Chang HW. Reactive oxygen species and autophagy modulation in non-marine drugs and marine drugs. Mar Drugs. 2014;12(11):5408–24.CrossRefPubMedPubMedCentral
45.
Palmeira dos Santos C, Pereira GJ, Barbosa CM, Jurkiewicz A, Smaili SS, Bincoletto C. Comparative study of autophagy inhibition by 3MA and CQ on Cytarabine induced death of leukaemia cells. J Cancer Res Clin Oncol. 2014;140(6):909–20.CrossRefPubMed
46.
Callus BA, Vaux DL. Caspase inhibitors: viral, cellular and chemical. Cell Death Differ. 2007;14(1):73–8.CrossRefPubMed
47.
Choi JM, Yoon BS, Lee SK, Hwang JK, Ryang R. Antioxidant properties of neohesperidin dihydrochalcone: inhibition of hypochlorous acid-induced DNA strand breakage, protein degradation, and cell death. Biol Pharm Bull. 2007;30(2):324–30.CrossRefPubMed
48.
Hu L, Li L, Xu D, Xia X, Pi R, Xu D, Wang W, Du H, Song E, Song Y. Protective effects of neohesperidin dihydrochalcone against carbon tetrachloride-induced oxidative damage in vivo and in vitro. Chem Biol Interact. 2014;213:51–9.CrossRefPubMed
Metadata
Title
Antiproliferation of Cryptocarya concinna-derived cryptocaryone against oral cancer cells involving apoptosis, oxidative stress, and DNA damage
Authors
Hsun-Shuo Chang
Jen-Yang Tang
Ching-Yu Yen
Hurng-Wern Huang
Chang-Yi Wu
Yi-An Chung
Hui-Ru Wang
Ih-Sheng Chen
Ming-Yii Huang
Hsueh-Wei Chang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1073-5

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