Efficacy of curcumin in inducing apoptosis and inhibiting the expression of VEGF in human pterygium fibroblasts

Lu,Cheng-Wei; Hao,Ji-Long; Yao,Lei; Li,Hai-Jun; Zhou,Dan-Dan

doi:10.3892/ijmm.2017.2944

Efficacy of curcumin in inducing apoptosis and inhibiting the expression of VEGF in human pterygium fibroblasts

Authors:
- Cheng-Wei Lu
- Ji-Long Hao
- Lei Yao
- Hai-Jun Li
- Dan-Dan Zhou
View Affiliations

Affiliations: Department of Ophthalmology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China , Department of Dermatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China , Translational Medicine Research Institute, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Radiology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: April 7, 2017 https://doi.org/10.3892/ijmm.2017.2944
Pages: 1149-1154
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Pterygium is an inflammatory and degenerative ocular surface disease, in which the conjunctiva on the cornea grows to form a fibrous tissue in the shape of a triangle. Although pterygium surgery is used broadly in clinical practice, its high recurrence rate poses a great concern for patients and doctors. In the present study, we examined the effects of curcumin on the apoptosis and proliferation of human pterygium fibroblasts (HPFs) in an in vitro culture system. HPFs were incubated with curcumin for 24 to 72 h (5, 20, 80 or 200 µmol/l). The proliferation-inhibiting effects of curcumin were assayed by MTT assay at different time points and at various concentrations. The expression of vascular endothelial growth factor (VEGF) in each group was detected by RT-qPCR and ELISA. The apoptotic effects of curcumin were detected by flow cytometry (FCM). Treatment with curcumin at 80 µmol/l for 48 h significantly inhibited HPF proliferation. Curcumin significant induced the apoptosis of HPFs. Our findings thus suggest that curcumin suppress cell proliferation in the pterygium by inducing HPF apoptosis and inhibiting VEGF expression. Thus, curcumin has potential for use as a novel agent for the treatment of pterygium in the near future.

View Figures

View References

1	Viso E, Gude F and Rodríguez-Ares MT: Prevalence of pinguecula and pterygium in a general population in Spain. Eye (Lond). 25:350–7. 2011. View Article : Google Scholar
2	Achigbu E and Ezepue UF: Prevalence and severity of pterygium among commercial motorcycle riders in South Eastern Nigeria. Ghana Med J. 48:153–157. 2014. View Article : Google Scholar
3	Asokan R, Venkatasubbu RS, Velumuri L, Lingam V and George R: Prevalence and associated factors for pterygium and pinguecula in a South Indian population. Ophthalmic Physiol Opt. 32:39–44. 2012. View Article : Google Scholar
4	Zhong H, Chen Q, Li J, Shen W, Sheng X, Niu Z, Zhou H, Wei T, Yuan Y and Pan CW: Ethnic variations in pterygium in a rural population in southwestern China: The Yunnan minority eye studies. Ophthalmic Epidemiol. 23:116–121. 2016. View Article : Google Scholar : PubMed/NCBI
5	Coroneo MT, Di Girolamo N and Wakefield D: The pathogenesis of pterygia. Curr Opin Ophthalmol. 10:282–288. 1999. View Article : Google Scholar
6	Threlfall TJ and English DR: Sun exposure and pterygium of the eye: a dose-response curve. Am J Ophthalmol. 128:280–287. 1999. View Article : Google Scholar : PubMed/NCBI
7	Chui J, Di Girolamo N, Wakefield D and Coroneo MT: The pathogenesis of pterygium: current concepts and their therapeutic implications. Ocul Surf. 6:24–43. 2008. View Article : Google Scholar : PubMed/NCBI
8	Anguria P, Kitinya J, Ntuli S and Carmichael T: The role of heredity in pterygium development. Int J Ophthalmol. 7:563–573. 2014.PubMed/NCBI
9	Bianchi E, Scarinci F, Grande C, Plateroti R, Plateroti P, Plateroti AM, Fumagalli L, Capozzi P, Feher J and Artico M: Immunohistochemical profile of VEGF, TGF-β and PGE₂ in human pterygium and normal conjunctiva: experimental study and review of the literature. Int J Immunopathol Pharmacol. 25:607–615. 2012. View Article : Google Scholar : PubMed/NCBI
10	Young CH, Lo YL, Tsai YY, Shih TS, Lee H and Cheng YW: CYP1A1 gene polymorphisms as a risk factor for pterygium. Mol Vis. 16:1054–1058. 2010.PubMed/NCBI
11	Kria L, Ohira A and Amemiya T: Growth factors in cultured pterygium fibroblasts: immunohistochemical and ELISA analysis. Graefes Arch Clin Exp Ophthalmol. 236:702–708. 1998. View Article : Google Scholar : PubMed/NCBI
12	Powers MR, Qu Z, O'Brien B, Wilson DJ, Thompson JE and Rosenbaum JT: Immunolocalization of bFGF in pterygia: association with mast cells. Cornea. 16:545–549. 1997. View Article : Google Scholar : PubMed/NCBI
13	Lee DH, Cho HJ, Kim JT, Choi JS and Joo CK: Expression of vascular endothelial growth factor and inducible nitric oxide synthase in pterygia. Cornea. 20:738–742. 2001. View Article : Google Scholar : PubMed/NCBI
14	Chen JK, Tsai RJ and Lin SS: Fibroblasts isolated from human pterygia exhibit transformed cell characteristics. In Vitro Cell Dev Biol Anim. 30A:243–248. 1994. View Article : Google Scholar : PubMed/NCBI
15	Maheshwari RK, Singh AK, Gaddipati J and Srimal RC: Multiple biological activities of curcumin: a short review. Life Sci. 78:2081–2087. 2006. View Article : Google Scholar : PubMed/NCBI
16	Zhang N, Li H, Jia J and He M: Anti-inflammatory effect of curcumin on mast cell-mediated allergic responses in ovalbumin-induced allergic rhinitis mouse. Cell Immunol. 298:88–95. 2015. View Article : Google Scholar : PubMed/NCBI
17	Kunnumakkara AB, Anand P and Aggarwal BB: Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 269:199–225. 2008. View Article : Google Scholar : PubMed/NCBI
18	Collaborative Ocular Melanoma Study Group: The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch Ophthalmol. 124:1684–1693. 2006. View Article : Google Scholar : PubMed/NCBI
19	Bimonte S, Barbieri A, Palma G, Rea D, Luciano A, D'Aiuto M, Arra C and Izzo F: Dissecting the role of curcumin in tumour growth and angiogenesis in mouse model of human breast cancer. BioMed Res Int. 2015:8781342015. View Article : Google Scholar : PubMed/NCBI
20	Khan N and Mukhtar H: Dietary agents for prevention and treatment of lung cancer. Cancer Lett. 359:155–164. 2015. View Article : Google Scholar : PubMed/NCBI
21	Chen A, Xu J and Johnson AC: Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene. 25:278–287. 2006.
22	Gupta SC, Patchva S and Aggarwal BB: Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 15:195–218. 2013. View Article : Google Scholar :
23	Amin AR, Haque A, Rahman MA, Chen ZG, Khuri FR and Shin DM: Curcumin induces apoptosis of upper aerodigestive tract cancer cells by targeting multiple pathways. PLoS One. 10:e01242182015. View Article : Google Scholar : PubMed/NCBI
24	Shi M, Cai Q, Yao L, Mao Y, Ming Y and Ouyang G: Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells. Cell Biol Int. 30:221–226. 2006. View Article : Google Scholar
25	Hong JH, Ahn KS, Bae E, Jeon SS and Choi HY: The effects of curcumin on the invasiveness of prostate cancer in vitro and in vivo. Prostate Cancer Prostatic Dis. 9:147–152. 2006. View Article : Google Scholar : PubMed/NCBI
26	Lu C, Song E, Hu DN, Chen M, Xue C, Rosen R and McCormick SA: Curcumin induces cell death in human uveal melanoma cells through mitochondrial pathway. Curr Eye Res. 35:352–360. 2010. View Article : Google Scholar : PubMed/NCBI
27	Zhang M, Bian F, Wen C and Hao N: Inhibitory effect of curcumin on proliferation of human pterygium fibroblasts. J Huazhong Univ Sci Technolog Med Sci. 27:339–342. 2007. View Article : Google Scholar : PubMed/NCBI
28	Yang SF, Lin CY, Yang PY, Chao SC, Ye YZ and Hu DN: Increased expression of gelatinase (MMP-2 and MMP-9) in pterygia and pterygium fibroblasts with disease progression and activation of protein kinase C. Invest Ophthalmol Vis Sci. 50:4588–4596. 2009. View Article : Google Scholar : PubMed/NCBI
29	Ribatti D, Nico B, Perra MT, Maxia C, Piras F, Murtas D, Crivellato E and Sirigu P: Correlation between NGF/TrkA and microvascular density in human pterygium. Int J Exp Pathol. 90:615–620. 2009. View Article : Google Scholar : PubMed/NCBI
30	Dos Reis GM, de P R Júnior A, E Silva KS, Rodrigues DA, Gomes MC, Martins JV, da Costa IR, Freitas GA and Moura KK: Pterygium in patients from Goiânia, Goiás, Brazil. Genet Mol Res. 14:6182–6188. 2015. View Article : Google Scholar : PubMed/NCBI
31	Shehzad A, Lee J and Lee YS: Curcumin in various cancers. Biofactors. 39:56–68. 2013. View Article : Google Scholar : PubMed/NCBI
32	Witkin JM and Li X: Curcumin, an active constiuent of the ancient medicinal herb Curcuma longa L.: some uses and the establishment and biological basis of medical efficacy. CNS Neurol Disord Drug Targets. 12:487–497. 2013. View Article : Google Scholar : PubMed/NCBI
33	Li Y and Zhang T: Targeting cancer stem cells by curcumin and clinical applications. Cancer Lett. 346:197–205. 2014. View Article : Google Scholar : PubMed/NCBI
34	Prasad S, Gupta SC, Tyagi AK and Aggarwal BB: Curcumin, a component of golden spice: from bedside to bench and back. Biotechnol Adv. 32:1053–1064. 2014. View Article : Google Scholar : PubMed/NCBI
35	Rahmani AH, Al Zohairy MA, Aly SM and Khan MA: Curcumin: a potential candidate in prevention of cancer via modulation of molecular pathways. Biomed Res Int. 2014:7616082014. View Article : Google Scholar : PubMed/NCBI
36	Han SS, Chung ST, Robertson DA, Ranjan D and Bondada S: Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc, bcl-XL, NF-κB, and p53. Clin Immunol. 93:152–161. 1999. View Article : Google Scholar : PubMed/NCBI
37	Mukherjee Nee Chakraborty S, Ghosh U, Bhattacharyya NP, Bhattacharya RK, Dey S and Roy M: Curcumin-induced apoptosis in human leukemia cell HL-60 is associated with inhibition of telomerase activity. Mol Cell Biochem. 297:31–39. 2007. View Article : Google Scholar
38	Shishodia S, Chaturvedi MM and Aggarwal BB: Role of curcumin in cancer therapy. Curr Probl Cancer. 31:243–305. 2007. View Article : Google Scholar : PubMed/NCBI
39	Li J, Zhang D, Stoner GD and Huang C: Differential effects of black raspberry and strawberry extracts on BaPDE-induced activation of transcription factors and their target genes. Mol Carcinog. 47:286–294. 2008. View Article : Google Scholar
40	Coussens LM and Werb Z: Matrix metalloproteinases and the development of cancer. Chem Biol. 3:895–904. 1996. View Article : Google Scholar : PubMed/NCBI
41	Tsai CH, Chiang YC, Chen HT, Huang PH, Hsu HC and Tang CH: High glucose induces vascular endothelial growth factor production in human synovial fibroblasts through reactive oxygen species generation. Biochim Biophys Acta. 1830:2649–2658. 2013. View Article : Google Scholar : PubMed/NCBI
42	Liu W, Sha X, Wen Y, Zhao W, Luo W and Hua Z: Effect of Avastin on the migration and invasion of pterygium fibroblasts. Eye Sci. 29:214–218. 2014.
43	Hosseini H, Nejabat M and Khalili MR: Bevacizumab (Avastin) as a potential novel adjunct in the management of pterygia. Med Hypotheses. 69:925–927. 2007. View Article : Google Scholar : PubMed/NCBI
44	Bahar I, Yeung SN, Sella R and Slomovic A: Anterior segment uses of bevacizumab. Curr Opin Ophthalmol. 23:303–316. 2012. View Article : Google Scholar : PubMed/NCBI
45	Hu A, Huang JJ, Jin XJ, Li JP, Tang YJ, Huang XF, Cui HJ, Xu WH and Sun GB: Curcumin suppresses invasiveness and vasculogenic mimicry of squamous cell carcinoma of the larynx through the inhibition of JAK-2/STAT-3 signaling pathway. Am J Cancer Res. 5:278–288. 2014.
46	Sun ZJ, Chen G, Zhang W, Hu X, Liu Y, Zhou Q, Zhu LX and Zhao YF: Curcumin dually inhibits both mammalian target of rapamycin and nuclear factor-κB pathways through a crossed phosphatidylinositol 3-kinase/Akt/IκB kinase complex signaling axis in adenoid cystic carcinoma. Mol Pharmacol. 79:106–118. 2011. View Article : Google Scholar