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Article

Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis

  • Authors:
    • Daniele Maggioni
    • Werner Garavello
    • Roberta Rigolio
    • Lorenzo Pignataro
    • Renato Gaini
    • Gabriella Nicolini
  • View Affiliations / Copyright

    Affiliations: Department of Surgery and Translational Medicine, University of Milan-Bicocca, I-20900 Monza, Italy, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, I-20122 Milan, Italy
  • Pages: 1675-1682
    |
    Published online on: August 21, 2013
       https://doi.org/10.3892/ijo.2013.2072
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Abstract

In the present study, we investigated the effect of apigenin, a flavonoid widely present in fruits and vegetables, on a tongue oral cancer-derived cell line (SCC-25) and on a keratinocyte cell line (HaCaT), with the aim of unveiling its antiproliferative mechanisms. The effect of apigenin on cell growth was evaluated by MTT assay, while apoptosis was investigated by phosphatidyl serine membrane translocation and cell cycle distribution by propidium iodide DNA staining through flow cytometry. In addition the expression of cyclins and cyclin-dependent kinases was evaluated by western blotting. A reduction of apigenin-induced cell growth was found in both cell lines, although SCC-25 cells were significantly more sensitive than the immortalized keratinocytes, HaCaT. Moreover, apigenin induced apoptosis and modulated the cell cycle in SCC-25 cells. Apigenin treatment resulted in cell cycle arrest at both G0/G1 and G2/M checkpoints, while western blot analysis revealed the decreased expression of cyclin D1 and E, and inactivation of CDK1 upon apigenin treatment. These results demonstrate the anticancer potential of apigenin in an oral squamous cell carcinoma cell line, suggesting that it may be a very promising chemopreventive agent due to its cancer cell cytotoxic activity and its ability to act as a cell cycle modulating agent at multiple levels.
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1. 

Jemal A, Siegel R, Xu J and Ward E: Cancer statistics. CA Cancer J Clin. 60:277–300. 2010.

2. 

Garavello W, Bertuccio P, Levi F, Lucchini F, Bosetti C, Malvezzi M, Negri E and La Vecchia C: The oral cancer epidemic in central and eastern Europe. Int J Cancer. 127:160–171. 2010. View Article : Google Scholar : PubMed/NCBI

3. 

Shiboski CH, Schmidt BL and Jordan RC: Tongue and tonsilar carcinoma: increasing trends in the US population ages 20–44 years. Cancer. 103:1843–1849. 2005.PubMed/NCBI

4. 

Bonifazi M, Malvezzi M, Bertuccio P, Edefonti V, Garavello W, Levi F, La Vecchia C and Negri E: Age-period-cohort analysis of oral cancer mortality in Europe: the end of an epidemic? Oral Oncol. 47:400–407. 2011. View Article : Google Scholar : PubMed/NCBI

5. 

Warnakulasuriya S: Living with oral cancer: epidemiology with particular reference to prevalence and life-style changes that influence survival. Oral Oncol. 46:407–410. 2010. View Article : Google Scholar : PubMed/NCBI

6. 

Rossi M, Garavello W, Talamini R, Negri E, Bosetti C, Dal Maso L, Lagiou P, Tavani A, Polesel J, Barzan L, Ramazzotti V, Franceschi S and La Vecchia C: Flavonoids and the risk of oral and pharyngeal cancer: a case-control study from Italy. Cancer Epidemiol Biomarkers Prev. 16:1621–1625. 2007. View Article : Google Scholar : PubMed/NCBI

7. 

Shukla S and Gupta S: Apigenin: a promising molecule for cancer prevention. Pharm Res. 27:962–978. 2010. View Article : Google Scholar : PubMed/NCBI

8. 

Patel D, Shukla S and Gupta S: Apigenin and cancer chemoprevention: progress, potential and promise (Review). Int J Oncol. 30:233–245. 2007.PubMed/NCBI

9. 

Gupta S, Afaq F and Mukhtar H: Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells. Biochem Biophys Res Commun. 287:914–920. 2001. View Article : Google Scholar : PubMed/NCBI

10. 

Choi EJ and Kim GH: Apigenin induces apoptosis through a mtochondria/caspase-pathway in human breast cancer MDA-MB-453 cells. J Clin Biochem Nutr. 44:260–265. 2009. View Article : Google Scholar : PubMed/NCBI

11. 

Zhong Y, Krisanapun C, Lee SH, Nualsanit T, Sams C, Peungvicha P and Baek SJ: Molecular targets of apigenin in colorectal cancer cells: involvement of p21, NAG-1 and p53. Eur J Cancer. 46:3365–3374. 2010. View Article : Google Scholar : PubMed/NCBI

12. 

Xu Y, Xin Y, Diao Y, Lu C, Fu J, Luo L and Yin Z: Synergistic effects of apigenin and paclitaxel on apoptosis of cancer cells. PLoS One. 6:e291692011. View Article : Google Scholar : PubMed/NCBI

13. 

Kaur P, Shukla S and Gupta S: Plant flavonoid apigenin inactivates Akt to trigger apoptosis in human prostate cancer: an in vitro and in vivo study. Carcinogenesis. 29:2210–2217. 2008. View Article : Google Scholar : PubMed/NCBI

14. 

Pandey M, Kaur P, Shukla S, Abbas A, Fu P and Gupta S: Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: in vitro and in vivo study. Mol Carcinog. 51:952–962. 2012. View Article : Google Scholar : PubMed/NCBI

15. 

Wei H, Tye L, Bresnick E and Birt DF: Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice. Cancer Res. 50:499–502. 1990.PubMed/NCBI

16. 

O’Prey J, Brown J, Fleming J and Harrison PR: Effects of dietary flavonoids on major signal transduction pathways in human epithelial cells. Biochem Pharmacol. 66:2075–2088. 2003.

17. 

Masuelli L, Marzocchella L, Quaranta A, Palumbo C, Pompa G, Izzi V, Canini A, Modesti A, Galvano F and Bei R: Apigenin induces apoptosis and impairs head and neck carcinomas EGFR/ErbB2 signaling. Front Biosci. 16:1060–1068. 2011. View Article : Google Scholar : PubMed/NCBI

18. 

Scott RE, Wilke MS, Wille JJ Jr, Pittelkow MR, Hsu BM and Kasperbauer JL: Human squamous carcinoma cells express complex defects in the control of proliferation and differentiation. Am J Pathol. 133:374–380. 1988.PubMed/NCBI

19. 

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

20. 

Komissarova EV and Rossman TG: Arsenite induced poly(ADP-ribosyl)ation of tumor suppressor P53 in human skin keratinocytes as a possible mechanism for carcinogenesis associated with arsenic exposure. Toxicol Appl Pharmacol. 243:399–404. 2010. View Article : Google Scholar

21. 

Lu HF, Chie YJ, Yang MS, Lee CS, Fu JJ, Yang JS, Tan TW, Wu SH, Ma YS, Ip SW and Chung JG: Apigenin induces caspase-dependent apoptosis in human lung cancer A549 cells through Bax- and Bcl-2-triggered mitochondrial pathway. Int J Oncol. 36:1477–1484. 2010.PubMed/NCBI

22. 

Abu-Yousif AO, Smith KA, Getsios S, Green KJ, Van Dross RT and Pelling JC: Enhancement of UVB-induced apoptosis by apigenin in human keratinocytes and organotypic keratinocyte cultures. Cancer Res. 68:3057–3065. 2008. View Article : Google Scholar : PubMed/NCBI

23. 

Ujiki MB, Ding XZ, Salabat MR, Bentrem DJ, Golkar L, Milam B, Talamonti MS, Bell RH Jr, Iwamura T and Adrian TE: Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest. Mol Cancer. 5:762006. View Article : Google Scholar : PubMed/NCBI

24. 

Lepley DM, Li B, Birt DF and Pelling JC: The chemopreventive flavonoid apigenin induces G2/M arrest in keratinocytes. Carcinogenesis. 17:2367–2375. 1996. View Article : Google Scholar : PubMed/NCBI

25. 

McVean M, Weinberg WC and Pelling JC: A p21(waf1)-independent pathway for inhibitory phosphorylation of cyclin-dependent kinase p34(cdc2) and concomitant G(2)/M arrest by the chemopreventive flavonoid apigenin. Mol Carcinog. 33:36–43. 2002. View Article : Google Scholar : PubMed/NCBI

26. 

Parker LL and Piwnica-Worms H: Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science. 257:1955–1957. 1992. View Article : Google Scholar : PubMed/NCBI

27. 

Casagrande F and Darbon JM: Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1. Biochem Pharmacol. 61:1205–1215. 2001. View Article : Google Scholar : PubMed/NCBI

28. 

Lepley DM and Pelling JC: Induction of p21/WAF1 and G1 cell-cycle arrest by the chemopreventive agent apigenin. Mol Carcinog. 19:74–82. 1997. View Article : Google Scholar : PubMed/NCBI

29. 

Shintani S, Mihara M, Nakahara Y, Kiyota A, Ueyama Y, Matsumura T and Wong DT: Expression of cell cycle control proteins in normal epithelium, premalignant and malignant lesions of oral cavity. Oral Oncol. 38:235–243. 2002. View Article : Google Scholar : PubMed/NCBI

30. 

Yamada S, Sumrejkanchanakij P, Amagasa T and Ikeda MA: Loss of cyclin E requirement in cell growth of an oral squamous cell carcinoma cell line implies deregulation of its downstream pathway. Int J Cancer. 111:17–22. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Maggioni D, Garavello W, Rigolio R, Pignataro L, Gaini R and Nicolini G: Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis. Int J Oncol 43: 1675-1682, 2013.
APA
Maggioni, D., Garavello, W., Rigolio, R., Pignataro, L., Gaini, R., & Nicolini, G. (2013). Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis. International Journal of Oncology, 43, 1675-1682. https://doi.org/10.3892/ijo.2013.2072
MLA
Maggioni, D., Garavello, W., Rigolio, R., Pignataro, L., Gaini, R., Nicolini, G."Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis". International Journal of Oncology 43.5 (2013): 1675-1682.
Chicago
Maggioni, D., Garavello, W., Rigolio, R., Pignataro, L., Gaini, R., Nicolini, G."Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis". International Journal of Oncology 43, no. 5 (2013): 1675-1682. https://doi.org/10.3892/ijo.2013.2072
Copy and paste a formatted citation
x
Spandidos Publications style
Maggioni D, Garavello W, Rigolio R, Pignataro L, Gaini R and Nicolini G: Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis. Int J Oncol 43: 1675-1682, 2013.
APA
Maggioni, D., Garavello, W., Rigolio, R., Pignataro, L., Gaini, R., & Nicolini, G. (2013). Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis. International Journal of Oncology, 43, 1675-1682. https://doi.org/10.3892/ijo.2013.2072
MLA
Maggioni, D., Garavello, W., Rigolio, R., Pignataro, L., Gaini, R., Nicolini, G."Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis". International Journal of Oncology 43.5 (2013): 1675-1682.
Chicago
Maggioni, D., Garavello, W., Rigolio, R., Pignataro, L., Gaini, R., Nicolini, G."Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis". International Journal of Oncology 43, no. 5 (2013): 1675-1682. https://doi.org/10.3892/ijo.2013.2072
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