Licochalcone B induces apoptosis of human oral squamous cell carcinoma through the extrinsic- and intrinsic-signaling pathways

  • Authors:
    • Hana Oh
    • Goo Yoon
    • Jae-Cheon Shin
    • Seon-Min Park
    • Seung-Sik Cho
    • Jin Hyoung Cho
    • Mee-Hyun Lee
    • Kangdong Liu
    • Young Sik Cho
    • Jung-Il Chae
    • Jung-Hyun Shim
  • View Affiliations

  • Published online on: February 1, 2016     https://doi.org/10.3892/ijo.2016.3365
  • Pages: 1749-1757
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Abstract

Licochalcone B (Lico B), which belongs to the retrochalcone family, is isolated from the roots of Chinese licorice. Lico B has been reported to have several other useful pharmacological properties, such as anti-inflammatory, antibacterial, antioxidant, antiulcer, anticancer, and anti-metastasis activities. We elucidated the underlying mechanism by which Lico B can induce apoptosis in oral squamous cell carcinoma (OSCC). Our results showed that exposure of OSCC cells (HN22 and HSC4) to Lico B significantly inhibited cell proliferation in a time- and concentration-dependent manner. Lico B caused cell cycle arrest at G1 phase along with downregulation of cyclin D1 and upregulation of p21 and p27 proteins. Lico B also facilitated the diffusion of phospholipid phosphatidylserine (PS) from inner to outer leaflets of the plasma membrane with chromatin condensation, DNA fragmentation, accumulated sub-G1 population in a concentration-dependent manner. Moreover, Lico B promoted the generation of reactive oxygen species (ROS), which, in turn, can induce CHOP, death receptor (DR) 4 and DR5. Lico B treatment induced downregulation of anti-apoptotic proteins (Bid and Bcl-xl and Mcl-1), and up­regulation of pro-apoptotic protein (Bax). Lico B also led to the loss of mitochondrial membrane potential (MMP), resulting in cytochrome c release. As can be expected from the above results, the apoptotic protease activating factor-1 (Apaf-1) and survivin were oppositely expressed in favor of apoptotic cell death. This notion was supported by the fact that Lico B activated multi-caspases with cleavage of poly (ADP-ribose) polymerase (PARP) protein. Therefore, it is suggested that Lico B is a promising drug for the treatment of human oral cancer via the induction of apoptotic cell death.

References

1 

Zeng G, Shen H, Yang Y, Cai X and Xun W: Licochalcone A as a potent antitumor agent suppresses growth of human oral cancer SCC-25 cells in vitro via caspase-3 dependent pathways. Tumour Biol. 35:6549–6555. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Neville BW and Day TA: Oral cancer and precancerous lesions. CA Cancer J Clin. 52:195–215. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Ni ZY, Lin FO, Liu DF and Xiao J: Decreased microRNA-143 expression and its tumor suppressive function in human oral squamous cell carcinoma. Genet Mol Res. 14:6943–6952. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Shin JA, Jung JY, Ryu MH, Safe S and Cho SD: Mithramycin A inhibits myeloid cell leukemia-1 to induce apoptosis in oral squamous cell carcinomas and tumor xenograft through activation of Bax and oligomerization. Mol Pharmacol. 83:33–41. 2013. View Article : Google Scholar

5 

Shin JA, Kim JS, Kwon KH, Nam JS, Jung JY, Cho NP and Cho SD: Apoptotic effect of hot water extract of Sanguisorba officinalis L. in human oral cancer cells. Oncol Lett. 4:489–494. 2012.

6 

Yuan X, Li T, Xiao E, Zhao H, Li Y, Fu S, Gan L and Wang Z, Zheng Q and Wang Z: Licochalcone B inhibits growth of bladder cancer cells by arresting cell cycle progression and inducing apoptosis. Food Chem Toxicol. 65:242–251. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Fu Y, Chen J, Li YJ, Zheng YF and Li P: Antioxidant and anti-inflammatory activities of six flavonoids separated from licorice. Food Chem. 141:1063–1071. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Furusawa J, Funakoshi-Tago M, Mashino T, Tago K, Inoue H, Sonoda Y and Kasahara T: Glycyrrhiza inflata-derived chalcones, Licochalcone A, Licochalcone B and Licochalcone D, inhibit phosphorylation of NF-kappaB p65 in LPS signaling pathway. Int Immunopharmacol. 9:499–507. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Park SY, Kim EJ, Choi HJ, Seon MR, Lim SS, Kang YH, Choi MS, Lee KW and Yoon Park JH: Anti-carcinogenic effects of non-polar components containing licochalcone A in roasted licorice root. Nutr Res Pract. 8:257–266. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Zhao H, Yuan X, Jiang J, Wang P, Sun X, Wang D and Zheng Q: Antimetastatic effects of licochalcone B on human bladder carcinoma T24 by inhibition of matrix metalloproteinases-9 and NF-κB activity. Basic Clin Pharmacol Toxicol. 115:527–533. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Lee MS, Cherla RP, Lentz EK, Leyva-Illades D and Tesh VL: Signaling through C/EBP homologous protein and death receptor 5 and calpain activation differentially regulate THP-1 cell maturation-dependent apoptosis induced by Shiga toxin type 1. Infect Immun. 78:3378–3391. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Zhu H, Liu XW, Ding WJ, Xu DQ, Zhao YC, Lu W, He QJ and Yang B: Up-regulation of death receptor 4 and 5 by celastrol enhances the anti-cancer activity of TRAIL/Apo-2L. Cancer Lett. 297:155–164. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Huang TT, Liu FG, Wei CF, Lu CC, Chen CC, Lin HC, Ojcius DM and Lai HC: Activation of multiple apoptotic pathways in human nasopharyngeal carcinoma cells by the prenylated isoflavone, osajin. PLoS One. 6:e183082011. View Article : Google Scholar : PubMed/NCBI

15 

Farooqi AA, Li KT, Fayyaz S, Chang YT, Ismail M, Liaw CC, Yuan SS, Tang JY and Chang HW: Anticancer drugs for the modulation of endoplasmic reticulum stress and oxidative stress. Tumour Biol. 36:5743–5752. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Xu L, Su L and Liu X: PKCδ regulates death receptor 5 expression induced by PS-341 through ATF4-ATF3/CHOP axis in human lung cancer cells. Mol Cancer Ther. 11:2174–2182. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Prasad S, Yadav VR, Ravindran J and Aggarwal BB: ROS and CHOP are critical for dibenzylideneacetone to sensitize tumor cells to TRAIL through induction of death receptors and down-regulation of cell survival proteins. Cancer Res. 71:538–549. 2011. View Article : Google Scholar :

18 

Wang Z, Liu Z, Cao Y, Paudel S, Yoon G and Cheon SH: Short and efficient synthesis of licochalcone B and D through acid-mediated Claisen-Schmidt condensation. Bull Korean Chem Soc. 34:3906–3908. 2013. View Article : Google Scholar

19 

Cho JJ, Chae JI, Yoon G, Kim KH, Cho JH, Cho SS, Cho YS and Shim JH: Licochalcone A, a natural chalconoid isolated from Glycyrrhiza inflata root, induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma. Int J Oncol. 45:667–674. 2014.PubMed/NCBI

20 

Janes SM, Ofstad TA, Campbell DH, Eddaoudi A, Warnes G, Davies D and Watt FM: PI3-kinase-dependent activation of apoptotic machinery occurs on commitment of epidermal keratinocytes to terminal differentiation. Cell Res. 19:328–339. 2009. View Article : Google Scholar :

21 

Fu HY, Okada K, Liao Y, Tsukamoto O, Isomura T, Asai M, Sawada T, Okuda K, Asano Y, Sanada S, et al: Ablation of C/EBP homologous protein attenuates endoplasmic reticulum-mediated apoptosis and cardiac dysfunction induced by pressure overload. Circulation. 122:361–369. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Shin DY, Park YS, Yang K, Kim GY, Kim WJ, Han MH, Kang HS and Choi YH: Decitabine, a DNA methyltransferase inhibitor, induces apoptosis in human leukemia cells through intracellular reactive oxygen species generation. Int J Oncol. 41:910–918. 2012.PubMed/NCBI

23 

Habibie YS, Yokoyama S, Abdelhamed S, Awale S, Sakurai H, Hayakawa Y and Saiki I: Survivin suppression through STAT3/β-catenin is essential for resveratrol-induced melanoma apoptosis. Int J Oncol. 45:895–901. 2014.PubMed/NCBI

24 

Kim YS, Kim EA, Park KG, Lee SJ, Kim MS, Sohn HY and Lee TJ: Dioscin sensitizes cells to TRAIL-induced apoptosis through downregulation of c-FLIP and Bcl-2. Oncol Rep. 28:1910–1916. 2012.PubMed/NCBI

25 

Law CK, Kwok HH, Poon PY, Lau CC, Jiang ZH, Tai WC, Hsiao WW, Mak NK, Yue PY and Wong RN: Ginsenoside compound K induces apoptosis in nasopharyngeal carcinoma cells via activation of apoptosis-inducing factor. Chin Med. 9:112014. View Article : Google Scholar : PubMed/NCBI

26 

Hearps AC, Burrows J, Connor CE, Woods GM, Lowenthal RM and Ragg SJ: Mitochondrial cytochrome c release precedes transmembrane depolarisation and caspase-3 activation during ceramide-induced apoptosis of Jurkat T cells. Apoptosis. 7:387–394. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Choi ES, Cho SD, Jeon JG and Cho NP: The apoptotic effect of the hexane extract of Rheum undulatum L. in oral cancer cells through the down-regulation of specificity protein 1 and survivin. Lab Anim Res. 27:19–24. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Mahapatra DK, Bharti SK and Asati V: Chalcone scaffolds as anti-infective agents: Structural and molecular target perspectives. Eur J Med Chem. 101:496–524. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Yalcin A, Clem BF, Imbert-Fernandez Y, Ozcan SC, Peker S, O'Neal J, Klarer AC, Clem AL, Telang S and Chesney J: 6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phos-phorylation of p27. Cell Death Dis. 5:e13372014. View Article : Google Scholar

30 

Alao JP: The regulation of cyclin D1 degradation: Roles in cancer development and the potential for therapeutic invention. Mol Cancer. 6:242007. View Article : Google Scholar : PubMed/NCBI

31 

Han MH, Lee WS, Jung JH, Jeong JH, Park C, Kim HJ, Kim G, Jung JM, Kwon TK, Kim GY, et al: Polyphenols isolated from Allium cepa L. induces apoptosis by suppressing IAP-1 through inhibiting PI3K/Akt signaling pathways in human leukemic cells. Food Chem Toxicol. 62:382–389. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN and Radi E: Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci. 322:254–262. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Kim IY, Kang YJ, Yoon MJ, Kim EH, Kim SU, Kwon TK, Kim IA and Choi KS: Amiodarone sensitizes human glioma cells but not astrocytes to TRAIL-induced apoptosis via CHOP-mediated DR5 upregulation. Neuro Oncol. 13:267–279. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Kim CD, Cha JD, Li S and Cha IH: The mechanism of acacetin-induced apoptosis on oral squamous cell carcinoma. Arch Oral Biol. 60:1283–1298. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Giam M, Huang DC and Bouillet P: BH3-only proteins and their roles in programmed cell death. Oncogene. 27(Suppl 1): S128–S136. 2008. View Article : Google Scholar

36 

Ola MS, Nawaz M and Ahsan H: Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem. 351:41–58. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Sha SH, Chen FQ and Schacht J: Activation of cell death pathways in the inner ear of the aging CBA/J mouse. Hear Res. 254:92–99. 2009. View Article : Google Scholar : PubMed/NCBI

38 

Hunter AM, LaCasse EC and Korneluk RG: The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis. 12:1543–1568. 2007. View Article : Google Scholar : PubMed/NCBI

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April 2016
Volume 48 Issue 4

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Copy and paste a formatted citation
APA
Oh, H., Yoon, G., Shin, J., Park, S., Cho, S., Cho, J.H. ... Shim, J. (2016). Licochalcone B induces apoptosis of human oral squamous cell carcinoma through the extrinsic- and intrinsic-signaling pathways. International Journal of Oncology, 48, 1749-1757. https://doi.org/10.3892/ijo.2016.3365
MLA
Oh, H., Yoon, G., Shin, J., Park, S., Cho, S., Cho, J. H., Lee, M., Liu, K., Cho, Y. S., Chae, J., Shim, J."Licochalcone B induces apoptosis of human oral squamous cell carcinoma through the extrinsic- and intrinsic-signaling pathways". International Journal of Oncology 48.4 (2016): 1749-1757.
Chicago
Oh, H., Yoon, G., Shin, J., Park, S., Cho, S., Cho, J. H., Lee, M., Liu, K., Cho, Y. S., Chae, J., Shim, J."Licochalcone B induces apoptosis of human oral squamous cell carcinoma through the extrinsic- and intrinsic-signaling pathways". International Journal of Oncology 48, no. 4 (2016): 1749-1757. https://doi.org/10.3892/ijo.2016.3365