Induced overexpression of CD44 associated with resistance to apoptosis on DNA damage response in human head and neck squamous cell carcinoma cells

Ohkoshi,Emika; Umemura,Naoki

doi:10.3892/ijo.2016.3821

Induced overexpression of CD44 associated with resistance to apoptosis on DNA damage response in human head and neck squamous cell carcinoma cells

Authors:
- Emika Ohkoshi
- Naoki Umemura
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Affiliations: Department of Natural and Medicinal Chemistry, Faculty of Pharmaceutical Sciences Aomori University, Aomori, Aomori 030-0943, Japan, Department of Oral Biochemistry, Asahi University School of Dentistry, Gifu 501-0296, Japan
Published online on: December 28, 2016 https://doi.org/10.3892/ijo.2016.3821
Pages: 387-395
Copyright: © Ohkoshi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

CD44 is a marker of cancer stem cells in head and neck squamous cell carcinoma, and CD44 expression is related to prognosis in cancer patients. We examined whether herbal medicine components affect CD44 expression and induce cancer cell apoptosis. Baicalin enhanced apoptosis with no effect on CD44 levels, while baicalein did not enhance apoptosis and upregulated CD44 in head and neck squamous cell carcinoma. Furthermore, baicalein induced phosphorylation of CHK1, as a marker of DNA damage response to S-to-G2/M phase arrest. Our results clearly demonstrated that baicalein enhanced expression of CD44 and accordingly enhanced the DNA damage response. These data suggest that induction of CD44 inhibited cancer cell induction of apoptosis by increasing the DNA damage response. Together, our findings suggest that CD44 expression in head and neck squamous cell carcinoma plays a role in enhancing the DNA damage response.

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1	Magee JA, Piskounova E and Morrison SJ: Cancer stem cells: Impact, heterogeneity, and uncertainty. Cancer Cell. 21:283–296. 2012. View Article : Google Scholar : PubMed/NCBI
2	Visvader JE and Lindeman GJ: Cancer stem cells: Current status and evolving complexities. Cell Stem Cell. 10:717–728. 2012. View Article : Google Scholar : PubMed/NCBI
3	Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD and Rich JN: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 444:756–760. 2006. View Article : Google Scholar : PubMed/NCBI
4	Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF and Ailles LE: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA. 104:973–978. 2007. View Article : Google Scholar : PubMed/NCBI
5	Zöller M: CD44: Can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 11:254–267. 2011. View Article : Google Scholar : PubMed/NCBI
6	Chikamatsu K, Ishii H, Takahashi G, Okamoto A, Moriyama M, Sakakura K and Masuyama K: Resistance to apoptosis-inducing stimuli in CD44⁺ head and neck squamous cell carcinoma cells. Head Neck. 34:336–343. 2012. View Article : Google Scholar
7	Harper LJ, Costea DE, Gammon L, Fazil B, Biddle A and Mackenzie IC: Normal and malignant epithelial cells with stem-like properties have an extended G2 cell cycle phase that is associated with apoptotic resistance. BMC Cancer. 10:1662010. View Article : Google Scholar : PubMed/NCBI
8	Joshua B, Kaplan MJ, Doweck I, Pai R, Weissman IL, Prince ME and Ailles LE: Frequency of cells expressing CD44, a head and neck cancer stem cell marker: Correlation with tumor aggressiveness. Head Neck. 34:42–49. 2012. View Article : Google Scholar
9	Orian-Rousseau V: CD44, a therapeutic target for metastasising tumours. Eur J Cancer. 46:1271–1277. 2010. View Article : Google Scholar : PubMed/NCBI
10	Li-Weber M: New therapeutic aspects of flavones: The anti-cancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev. 35:57–68. 2009. View Article : Google Scholar
11	Zha LH, He LS, Lian FM, Zhen Z, Ji HY, Xu LP and Tong XL: Clinical strategy for optimal traditional Chinese medicine (TCM) herbal dose selection in disease therapeutics: Expert consensus on classic TCM herbal formula dose conversion. Am J Chin Med. 43:1515–1524. 2015. View Article : Google Scholar : PubMed/NCBI
12	Peng H, He Y, Zheng G, Zhang W, Yao Z and Xie W: Meta-analysis of traditional herbal medicine in the treatment of nonalcoholic fatty liver disease. Cell Mol Biol (Noisy-le-grand). 62:88–95. 2016.
13	Sumino M, Saito Y, Ikegami F, Hirasaki Y and Namiki T: Extraction efficiency of shosaikoto (xiaochaihu tang) and investigation of the major constituents in the residual crude drugs. Evid Based Complement Alternat Med. 2012:8905242012. View Article : Google Scholar : PubMed/NCBI
14	He JX, Ohno K, Tang J, Hattori M, Tani T and Akao T: Da-Chaihu-Tang alters the pharmacokinetics of nifedipine in rats and a treatment regimen to avoid this. J Pharm Pharmacol. 66:1623–1630. 2014. View Article : Google Scholar : PubMed/NCBI
15	Kato S, Hayashi S, Kitahara Y, Nagasawa K, Aono H, Shibata J, Utsumi D, Amagase K and Kadowaki M: Saireito (TJ-114), a Japanese traditional herbal medicine, reduces 5-fluorouracil-induced intestinal mucositis in mice by inhibiting cytokine-mediated apoptosis in intestinal crypt cells. PLoS One. 10:e01162132015. View Article : Google Scholar : PubMed/NCBI
16	Su SB, Xie MJ, Sawabu N and Motoo Y: Suppressive effect of herbal medicine saikokeishito on acinar cell apoptosis in rat spontaneous chronic pancreatitis. Pancreatology. 7:28–36. 2007. View Article : Google Scholar : PubMed/NCBI
17	Iijima H, Daikonya A, Takamatsu S, Kanno A, Magariyama K, Yoshikawa K, Takamiya T, Ueda Y, Yakubo S, Matsumoto T, et al: Effects of the herbal medicine composition 'Saiko-ka-ryukotsu-borei-To' on the function of endothelial progenitor cells in hypertensive rats. Phytomedicine. 20:196–201. 2013. View Article : Google Scholar
18	Nakayama T, Suzuki S, Kudo H, Sassa S, Nomura M and Sakamoto S: Effects of three Chinese herbal medicines on plasma and liver lipids in mice fed a high-fat diet. J Ethnopharmacol. 109:236–240. 2007. View Article : Google Scholar
19	Ben-Arye E, Mahajna J, Aly R, Ali-Shtayeh MS, Bentur Y, Lev E, Deng G and Samuels N: Exploring an herbal 'wonder cure' for cancer: A multidisciplinary approach. J Cancer Res Clin Oncol. 142:1499–1508. 2016. View Article : Google Scholar : PubMed/NCBI
20	Chung VC, Wu X, Lu P, Hui EP, Zhang Y, Zhang AL, Lau AY, Zhao J, Fan M, Ziea ET, et al: Chinese herbal medicine for symptom management in cancer palliative care: Systematic review and meta-analysis. Medicine (Baltimore). 95:e27932016. View Article : Google Scholar
21	Ohtake N, Nakai Y, Yamamoto M, Sakakibara I, Takeda S, Amagaya S and Aburada M: Separation and isolation methods for analysis of the active principles of Sho-saiko-to (SST) oriental medicine. J Chromatogr B Analyt Technol Biomed Life Sci. 812:135–148. 2004. View Article : Google Scholar : PubMed/NCBI
22	Yoshie F, Iizuka A, Komatsu Y, Matsumoto A, Itakura H and Kondo K: Effects of Dai-saiko-to (Da-Chai-Hu-Tang) on plasma lipids and atherosclerotic lesions in female heterozygous heritable Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Pharmacol Res. 50:223–230. 2004. View Article : Google Scholar : PubMed/NCBI
23	Kishida Y, Miki H, Nishii T, Inoue T, Nishida S, Yoshikawa H and Sugano N: Therapeutic effects of Saireito (TJ-114), a traditional Japanese herbal medicine, on postoperative edema and inflammation after total hip arthroplasty. Phytomedicine. 14:581–586. 2007. View Article : Google Scholar : PubMed/NCBI
24	Ohta Y, Kongo-Nishimura M, Hayashi T, Kitagawa A, Matsura T and Yamada K: Saikokeishito extract exerts a therapeutic effect on α-naphthylisothiocyanate-induced liver injury in rats through atenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. J Clin Biochem Nutr. 40:31–41. 2007. View Article : Google Scholar
25	Yoshie F, Iizuka A, Kubo M, Komatsu Y, Matsumoto A, Itakura H, Takeda H, Matsumiya T and Kondo K: Protective effects of Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) against atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Pharmacol Res. 43:481–488. 2001. View Article : Google Scholar : PubMed/NCBI
26	Ohkoshi E, Nagashima T, Sato H, Fujii Y, Nozawa K and Nagai M: Simple preparation of baicalin from Scutellariae Radix. J Chromatogr A. 1216:2192–2194. 2009. View Article : Google Scholar
27	Umemura N, Zhu J, Mburu YK, Forero A, Hsieh PN, Muthuswamy R, Kalinski P, Ferris RL and Sarkar SN: Defective NF-κB signaling in metastatic head and neck cancer cells leads to enhanced apoptosis by double-stranded RNA. Cancer Res. 72:45–55. 2012. View Article : Google Scholar
28	Trinh HT, Joh EH, Kwak HY, Baek NI and Kim DH: Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice. Acta Pharmacol Sin. 31:718–724. 2010. View Article : Google Scholar : PubMed/NCBI
29	Takahashi H, Chen MC, Pham H, Angst E, King JC, Park J, Brovman EY, Ishiguro H, Harris DM, Reber HA, et al: Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells. Biochim Biophys Acta. 1813:1465–1474. 2011. View Article : Google Scholar : PubMed/NCBI
30	Donald G, Hertzer K and Eibl G: Baicalein - an intriguing therapeutic phytochemical in pancreatic cancer. Curr Drug Targets. 13:1772–1776. 2012. View Article : Google Scholar : PubMed/NCBI
31	Naveenkumar C, Asokkumar S, Raghunandhakumar S, Jagan S, Anandakumar P, Augustine TA, Kamaraj S and Devaki T: Potent antitumor and antineoplastic efficacy of baicalein on benzo(a) pyrene-induced experimental pulmonary tumorigenesis. Fundam Clin Pharmacol. 26:259–270. 2012. View Article : Google Scholar
32	Weiss JM, Bagley S, Hwang WT, Bauml J, Olson JG, Cohen RB, Hayes DN and Langer C: Capecitabine and lapatinib for the first-line treatment of metastatic/recurrent head and neck squamous cell carcinoma. Cancer. 122:2350–2355. 2016. View Article : Google Scholar : PubMed/NCBI
33	Kurokawa M, Ise N, Omi K, Goishi K and Higashiyama S: Cisplatin influences acquisition of resistance to molecular-targeted agents through epithelial-mesenchymal transition-like changes. Cancer Sci. 104:904–911. 2013. View Article : Google Scholar : PubMed/NCBI
34	Chappell J and Dalton S: Altered cell cycle regulation helps stem-like carcinoma cells resist apoptosis. BMC Biol. 8:632010. View Article : Google Scholar : PubMed/NCBI
35	Schreiber V, Dantzer F, Ame JC and de Murcia G: Poly(ADP-ribose): Novel functions for an old molecule. Nat Rev Mol Cell Biol. 7:517–528. 2006. View Article : Google Scholar : PubMed/NCBI