Abstract
Dysadherin is a recently found anti-adhesion molecule, therefore detection and down regulation of its expression is promising in cancer treatment. The up-regulation of dysadherin contributes to colon cancer recurrence and metastasis. Dysadherin also has connections with cytoskeletal proteins and it can cause alterations in the organisation of filamentous actin (F-actin) in metastatic cancers. In this study, hypericin (HYP)-mediated photodynamic therapy (PDT) was performed in two different grade colon adenocarcinoma cell lines HT-29 (Grade I) and Caco-2 (Grade II). Cells were treated with 0.04, 0.08 or 0.15 μM HYP concentrations and irradiated with (4 J/cm2) fluorescent lamps. The effects of HYP was examined 16 and 24 h after the activation. We investigated for the first time the effect of HYP-mediated PDT on the expression of dysadherin and F-actin organisation. According to the results, HYP mediated PDT caused a decrease in gene expression and immunofluorescence staining of dysadherin and an increase in actin stress fibers and actin aggregates in HT-29 and Caco-2 cell lines. Besides, cytotoxicity, number of floating cells and apoptotic index changed depending on the cell type, HYP concentration and incubation time. We have demonstrated for the first time that dysadherin and F-actin could be target molecules for HYP-mediated PDT in HT-29 and Caco-2 colon cancer cell lines.
Similar content being viewed by others
References
Ackroyd R, Kelty C, Brown N, Reed M (2001) The history of photodetection and photodynamic therapy. Photochem Photobiol 74:656–669
Allison RR, Sibata CH (2010) Oncologic photodynamic therapy photosensitizers: a clinical review. Photodiagnosis Photodyn 7:61–75
Aoki S, Shimamura T, Shibata T, Nakanishi Y, Moriya Y, Sato Y, Kitajima M, Sakamoto M, Hirohashi S (2003) Prognostic significance of dysadherin expression in advanced colorectal carcinoma. Br J Cancer 88:726–732
Ashkenazi A (2002) Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Drug Discov 2:420–430
Batistatou A, Charalabopoulos AK, Scopa CD, Nakanishi Y, Kappas A, Hirohashi S, Agnantis NJ, Charalabopoulos K (2006) Expression patterns of dysadherin and E-cadherin in lymph node metastases of colorectal carcinoma. Virchows Arch 448:763–767
Blank M, Mandel M, Keisari Y, Meruelo D, Lavie G (2003) Enhanced ubiquitinylation of heat shock protein 90 as a potential mechanism for mitotic cell death in cancer cells induced with hypericin. Cancer Res 63:8241–8247
Buda A, Pignatelli M (2004) Cytoskeletal network in colon cancer: from genes to clinical application. Int J Biochem Cell Biol 36:759–765
Chaturvedi V, Sreedhar AS (2010) Hsp90 inhibition induces destabilization of actin cytoskeleton in tumor cells: Functional significance of Hsp90 interaction with F-actin. Asian Pac J Trop Med 3:715–722
Coates TD, Watts RG, Hartman R, Howard TH (1992) Distribution to development of polar shape in human polymorphonuclear neutrophils. J Cell Biol 117:765–774
Dahl JE, Mary J, Frangou-Polyzois MJ, Polyzois GL (2006) In vitro biocompatibility of denture relining materials. Gerodontology 23:17–22
Di Venosa G, Rodriguez L, Mamone L, Gándara L, Rossetti MV, Batlle A, Casas A (2012) Changes in actin and E-cadherin expression induced by 5-aminolevulinic acid photodynamic therapy in normal and ras-transfected human mammary cell lines. J Photochem Photobiol B Biol 106:47–52
Galanou MC, Theodossiou TA, Tsiourvas D, Sideratou Z, Paleos CM (2008) Interactive transport, subcellular relocation and enhanced phototoxicity of hypericin encapsulated in guanidinylated liposomes via molecular recognition. Photochem Photobiol 84:1073–1083
Grzanka A, Grzanka D, Orlikowska M (2003) Cytoskeletal reorganization during process of apoptosis induced by cytostatic drugs in K-562 and HL-60 leukemia cell lines. Biochem Pharmacol 66:1611–1617
Hendrickx N, Volanti C, Moens U, Seternes OM, de Witte P, Vandenheede JR, Piette J, Agostinis P (2003) Up-regulation of cyclooxygenase-2 and apoptosis resistance by p38 MAPK in hypericin-mediated photodynamic therapy of human cancer cells. J Biol Chem 278:52231–52239
Hirohashi S, Kanai Y (2003) Cell adhesion system and human cancer morphogenesis. Cancer Sci 94:575–581
Ino Y, Gotoh M, Sakamoto M, Tsukagoshi K, Hirohashi S (2002) Dysadherin a cancer associated cell membrane glycoprotein, down regulates E-cadherin and promotes metastasis. Med Sci 99:365–370
Jendzelovsky R, Mike J, Koval K, Soucek K, Procházková J, Kello M, Saková V, Hofmanová J, Kozubík A, Fedoroko P (2009) Drug efflux transporters, MRP1 and BCRP, affect the outcome of hypericin-mediated photodynamic therapy in HT-29 adenocarcinoma cells. Photochem Photobiol Sci 8:1716–1723
Kamuhabwa AR, Augustijns P, de Witte PA (1999) In vitro transport and uptake of protohypericin and hypericin in the Caco-2 model. Int J Pharm 188:81–86
Kaplan JH (2005) A moving new role for the sodium pump in epithelial cells and carcinomas. Sci STKE 289:31
Korb T, Schlüter K, Enns A, Spiegel HU, Senninger N, Nicolson GL, Haier J (2004) Integrity of actin fibers and microtubules influences metastatic tumor cell adhesion. Exp Cell Res 299:236–247
Ku GR, Tan LBH, Yau T, Boku N, Laohavinij S, Cheng AL, Kang YK, Lopes GL (2012) Management of colon cancer: resource-stratified guidelines from the Asian oncology. Lancet Oncol 13:e470–e481
Lev-Ari S, Strier L, Kazanov D, Shapiro LM, Sobol HD, Pinchuk I, Marian B, Lichtenberg D, Arber N (2005) Celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells. Clin Cancer Res 11:6738–6744
Mikeš J, Kleban J, Saèková V, Horváth V, Jamborová E, Vaculová A, Kozubík A, Hofmanová J, Fedoroèko P (2007) Necrosis predominates in the cell death of human colon adenocarcinoma HT-29 cells treated under variable conditions of photodynamic therapy with hypericin. Photochem Photobiol Sci 6:758–766
Mitchell DM, Ball JM (2004) Characterization of a spontaneously polarizing HT-29 cell line, HT-29/cl.f8. In Vitro Cell Dev Anim 40:297–301
Nam JS, Hirohashi S, Wakefield LM (2007) Dysadherin: a new player in cancer progression. Cancer Lett 255:161–169
Park JR, Kim RJ, Lee YK, Kim SR, Roh KJ, Oh SH, Kong G, Kang KS, Nam JS (2011) Dysadherin can enhance tumorigenesis by conferring properties of stem-like cells to hepatocellular carcinoma cells. J Hepatol 54:122–131
Paszkoa E, Ehrhardt C, Senge MO, Kelleher DP, Reynolds JV (2011) Nanodrug applications in photodynamic therapy. Photodiagnosis Photodyn 8:14–29
Ray RM, Bhattacharya S, Johnson LR (2011) Mdm2 inhibition induces apoptosis in p53 deficient humancolon cancer cells by activating p73-and E2F1mediatedexpression of PUMA and Siva-1. Apoptosis 16:35–44
Reed JC (1998) Bcl-2 family proteins. Oncogene 17:3225–3236
Salvador A (2008) Investigation about the mechanism of action of new antiproliferative compounds. Ph.D. thesis. Universita’ Degli Studi Di Padova
Sanovic R, Verwanger T, Hartl A, Krammer B (2011) Low dose hypericin-PDT induces complete tumor regression in BALB/c mice bearing CT26 colon carcinoma. Photodiagnosis Photodyn Ther 8:291–296
Šemelakova M, Mikeš J, Jendzelovsky R, Fedorocko P (2012) The pro-apoptotic and anti-invasive effects of hypericin-mediated photodynamic therapy are enhanced by hyperforin or aristoforin in HT-29 colon adenocarcinoma cells. J Photochem Photobiol B Biol 117:115–125
Shimamura T, Yasuda J, Ino Y, Gotoh M, Tsuchiya A, Nakajima A, Sakamoto M, Kanai Y, Hirohashi S (2004) Dysadherin expression facilitates cell motility and metastatic potential of human pancreatic cancer cells. Cancer Res 64:6989–6995
Theodossiou TA, Hothersall JS, De Witte PA, Pantos A, Agostinis P (2009) The multifaceted photocytotoxic profile of hypericin. Mol Pharm 6:1775–1789
Wicki A, Lehembre F (2006) Tumor invasion in the absence of epithelialmesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Cancer Cell 9:261–272
Yamazaki T, Yamazaki I, Nishimura Y, Dai R, Song PS (1993) Time-resolved fluorescence spectroscopy and photolysis of the photoreceptor blepharismin. Biochim Biophys Acta 1143:319–326
Yamazaki D, Kurisu S, Takenawa T (2005) Regulation of cancer cell motility through actin reorganization. Cancer Sci 96:379–386
Yang ZR, Liu M, Peng XL, Zhang JX, Dong WG (2012) Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro. Biochem Biophys Res Commun 421:627–633
Yoo JO, Ha KS (2012) New insights into the mechanisms for photodynamic therapy-induced cancer cell death. Int Rev Cel Mol Bio 295:139–174
Acknowledgments
This research was supported by Hacettepe University Scientific Research Projects Coordination Unit (09 01 601 011) and it is a part of phD thesis of Aysun Kılıç Süloğlu. The authors want to thank Şükran Yılmaz, Hande Canpınar, Çağatay Karaaslan for their help in the analysis and sharing their experiences.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kılıç Süloğlu, A., Selmanoğlu, G. & Akay, M.T. Alterations in dysadherin expression and F-actin reorganization: a possible mechanism of hypericin-mediated photodynamic therapy in colon adenocarcinoma cells. Cytotechnology 67, 311–330 (2015). https://doi.org/10.1007/s10616-013-9688-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10616-013-9688-6