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Planta Med 2013; 79(14): 1298-1306
DOI: 10.1055/s-0033-1350619
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Growth Inhibition and Apoptosis-Inducing Effects of Cudraflavone B in Human Oral Cancer Cells via MAPK, NF-κB, and SIRT1 Signaling Pathway

Hwa-Jeong Lee   *
1   Department of Maxillofacial Tissue Regeneration and Research Center for Tooth & Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea,
,
Q-Schick Auh   *
2   Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea
,
Young-Man Lee
1   Department of Maxillofacial Tissue Regeneration and Research Center for Tooth & Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea,
,
Soo-Kyung Kang
2   Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea
,
Seok-Woo Chang
3   Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea
,
Dong-Sung Lee
4   College of Pharmacy, Wonkwang University, Iksan, Republic of Korea
,
Youn-Chul Kim
4   College of Pharmacy, Wonkwang University, Iksan, Republic of Korea
,
Eun-Cheol Kim
1   Department of Maxillofacial Tissue Regeneration and Research Center for Tooth & Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea,
› Author Affiliations
Further Information

Publication History

received 20 February 2013
revised 19 June 2013

accepted 24 June 2013

Publication Date:
23 July 2013 (online)

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Growth Inhibition and Apoptosis-Inducing Effects of Cudraflavone B in Human Oral Cancer Cells via MAPK, NF-κB, and SIRT1 Signaling PathwayPlanta Med 2013; 79(14): E3-E3
DOI: 10.1055/s-0033-1350778

Abstract

The goal of this study was to investigate the effect and molecular mechanism of cudraflavone B, a prenylated flavonoid isolated from the root bark of Cudrania tricuspidata, against oral squamous cell carcinoma cells. We observed that cudraflavone B inhibited proliferation of these cells in a time- and dose-dependent manner. At 15 µM, cudraflavone B induced cell death via apoptosis (characterized by the appearance of nuclear morphology) and increased the accumulation of the sub-G1 peak (portion of apoptotic annexin V positive cells). Treatment with cudraflavone B triggered the mitochondrial apoptotic pathway (indicated by induction of the proapoptotic protein p53 and the p21 and p27 effector proteins), downregulation of cell cycle regulatory proteins (e.g., p-Rb, changing Bax/Bcl-2 ratios, cytochrome-c release), and caspase-3 activation. Cudraflavone B time-dependently activated NF-κB, the MAP kinases p38, and ERK, and induced the expression of SIRT1. SIRT1 activator, resveratrol, dose-dependently attenuated the growth-inhibitory and apoptosis-inducing effect of cudraflavone B and blocked cudraflavone B-induced regulatory protein expressions in the mitochondrial pathway such as p53, p21, p27, Bax, caspase-3, and cytochrome-c. Conversely, treatment with SIRT1 inhibitor sirtinol caused opposite effects. These results demonstrate for the first time that the molecular mechanism underlying the antitumor effect in oral squamous cell carcinoma cells is related to the activation of MAPK/and NF-κB as well as of the SIRT1 pathway. Therefore, cudraflavone B may be a lead for the development of a potential candidate for human oral squamous cell carcinoma cells.

Key words

cudraflavone B - Cudrania tricuspidata - Moraceae - oral cancer cell - apoptosis - NF-κB - SIRT1

* Contributed equally to this work as 1st authors.


 

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