Down-regulation of heat-shock protein 27–induced resistance to photodynamic therapy in oral cancer cells
Jisun Kim
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
These authors contributed equally to this work.
Search for more papers by this authorHyuncheol Jung
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
These authors contributed equally to this work.
Search for more papers by this authorWonbong Lim
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorSangwoo Kim
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorYoungjong Ko
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorSandeep Karna
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorOksu Kim
Department of Periodontics, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorYooduk Choi
Department of Pathology, Faculty of Medicine, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorHongran Choi
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorOkjoon Kim
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorJisun Kim
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
These authors contributed equally to this work.
Search for more papers by this authorHyuncheol Jung
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
These authors contributed equally to this work.
Search for more papers by this authorWonbong Lim
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorSangwoo Kim
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorYoungjong Ko
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorSandeep Karna
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorOksu Kim
Department of Periodontics, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorYooduk Choi
Department of Pathology, Faculty of Medicine, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorHongran Choi
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorOkjoon Kim
Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea
Search for more papers by this authorAbstract
Photodynamic therapy (PDT) of cells is a new treatment modality involving selective delivery of a photosensitive dye into target cells, followed by visible light irradiation. PDT induces cell death by excessive ROS generation. The effects of multiple photosensitizers were owing to the difference in cell types involving sensitizer-specific protein changes linked to resistance. HSP27 is regulated in response to stress and is associated with apoptotic process. The effects of HSP27 on PDT resistance are controversial and unclear. The purpose of this study was to investigate the role of HSP27 down-regulation in the PDT-induced cells and HSP27 regulation in the resistance to PDT. KB cells transfected with HSP27 siRNA were exposed to hematoporphyrin (HP) followed by irradiation at 635 nm at an energy density of 4.5 mW/cm2. After irradiation, the effects on HSP27 down-regulation were assessed by MTT assay, flow cytometry, confocal analysis, Western blotting and caspase activity. The results of this study showed that down-regulation of HSP27 restored cell survival in HP-PDT-induced apoptotic KB cells. HSP27 down-regulation attenuated PDT-induced apoptosis through caspase-mediated pathway in KB cells. Also, HSP27 silencing regulated Bax, Bcl-2, and PARP protein expression in PDT-induced cells. Therefore, HSP27 down-regulation confers resistance to PDT through interruption of apoptotic protein activity in PDT-induced cell death. HSP27 might contribute to regulating PDT-induced apoptosis in PDT-resistant cells.
References
- 1Van duijnhoven FH, Aalbers RI, Rovers JP, et al.The immunological consequences of photodynamic treatment of cancer, a literature review. Immunobiology2003; 207: 105–13.
- 2Chen HM, Chen CT, Yang H, et al.Successful treatment of an extensive verrucous carcinoma with topical 5-aminolevulinic acid-mediated photodynamic therapy. J Oral Pathol Med2005; 34: 253–6.
- 3Dolmans DE, Fukumura D. Jain RK Photodynamic therapy for cancer. Nat Rev Cancer2003; 3: 380–7.
- 4Mccaughan JS Jr, Ellison EC, Guy JT, et al.Photodynamic therapy for esophageal malignancy: a prospective twelve-year studyAnn Thorac Surg1996; 62: 1005–9, discussion 1009-10.
- 5Ell CClinical photodynamic therapy: where is it heading?Endoscopy1998; 30: 408–11.
- 6Maier A, Tomaselli F, Gebhard F, et al.Palliation of advanced esophageal carcinoma by photodynamic therapy and irradiationAnn Thorac Surg2000; 69: 1006–9.
- 7Kessel DPhotodynamic therapy and neoplastic diseaseOncol Res1992; 4: 219–25.
- 8Henderson BW, Dougherty TJHow does photodynamic therapy work?Photochem Photobiol1992; 55: 145–57.
- 9Buytaert E, Dewaele M, Agostinis PMolecular effectors of multiple cell death pathways initiated by photodynamic therapyBiochim Biophys Acta2007; 1776: 86–107.
- 10Zhao H, Xing D, Chen QNew insights of mitochondria reactive oxygen species generation and cell apoptosis induced by low dose photodynamic therapyEur J Cancer2011; 47: 2750–61.
- 11Oleinick NL, Evans HHThe photobiology of photodynamic therapy: cellular targets and mechanismsRadiat Res1998; 150: S146–56.
- 12Choi H, Lim W, Kim JE, et al.Cell death and intracellular distribution of hematoporphyrin in a KB cell linePhotomed Laser Surg2009; 27: 453–60.
- 13Chu ES, Wu RW, Yow CM, et al.The cytotoxic and genotoxic potential of 5-aminolevulinic acid on lymphocytes: a comet assay studyCancer Chemother Pharmacol2006; 58: 408–14.
- 14Calzavara-pinton PG, Venturini M, Sala RPhotodynamic therapy: update 2006 Part 1: Photochemistry and photobiologyJ Eur Acad Dermatol Venereol2007; 21: 293–302.
- 15Ibbotson SHAdverse effects of topical photodynamic therapyPhotodermatol Photoimmunol Photomed2011; 27: 116–30.
- 16Wolf P, Fink-puches R, Reimann-weber A, et al.Development of malignant melanoma after repeated topical photodynamic therapy with 5-aminolevulinic acid at the exposed siteDermatology1997; 194: 53–4.
- 17Wennberg AM, Stenquist B, Stockfleth E, et al.Photodynamic therapy with methyl aminolevulinate for prevention of new skin lesions in transplant recipients: a randomized studyTransplantation2008; 86: 423–9.
- 18Hayami J, Okamoto H, Sugihara A, et al.Immunosuppressive effects of photodynamic therapy by topical aminolevulinic acidJ Dermatol2007; 34: 320–7.
- 19Finlan LE, Kernohan NM, Thomson G, et al.Differential effects of 5-aminolaevulinic acid photodynamic therapy and psoralen + ultraviolet A therapy on p53 phosphorylation in normal human skin in vivoBr J Dermatol2005; 153: 1001–10.
- 20Sanovic R, Krammer B, Grumboeck S, et al.Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericinInt J Oncol2009; 35: 921–39.
- 21Shen XY, Zacal N, Singh G, et al.Alterations in mitochondrial and apoptosis-regulating gene expression in photodynamic therapy-resistant variants of HT29 colon carcinoma cellsPhotochem Photobiol2005; 81: 306–13.
- 22Wang HP, Hanlon JG, Rainbow AJ, et al.Up-regulation of Hsp27 plays a role in the resistance of human colon carcinoma HT29 cells to photooxidative stressPhotochem Photobiol2002; 76: 98–104.
- 23Di domenico F, Sultana R, Tiu GF, et al.Protein levels of heat shock proteins 27, 32, 60, 70, 90 and thioredoxin-1 in amnestic mild cognitive impairment: an investigation on the role of cellular stress response in the progression of Alzheimer diseaseBrain Res2010; 1333: 72–81.
- 24Mayhew S, Vernon DI, Schofield J, et al.Investigation of cross-resistance to a range of photosensitizers, hyperthermia and UV light in two radiation-induced fibrosarcoma cell strains resistant to photodynamic therapy in vitroPhotochem Photobiol2001; 73: 39–46.
- 25Singh G, Espiritu M, Shen XY, et al. In vitro induction of PDT resistance in HT29, HT1376 and SK-N-MC cells by various photosensitizersPhotochem Photobiol2001; 73: 651–6.
- 26Huang H, Zhao X, Chen Y, et al.Apoptosis induced by ZnPcH1-based photodynamic therapy in Jurkat cells and HEL cellsInt J Hematol2011; 94: 539–44.
- 27Gollnick SO, Owczarczak B, Maier PPhotodynamic therapy and anti-tumor immunityLasers Surg Med2006; 38: 509–15.
- 28Ferrario A, Chantrain CF, Von Tiehl K, et al.The matrix metalloproteinase inhibitor prinomastat enhances photodynamic therapy responsiveness in a mouse tumor modelCancer Res2004; 64: 2328–32.
- 29Kim SC, Stice JP, Chen L, et al.Extracellular heat shock protein 60, cardiac myocytes, and apoptosisCirc Res2009; 105: 1186–95.
- 30Luo X, Zuo X, Zhou Y, et al.Extracellular heat shock protein 70 inhibits tumour necrosis factor-alpha induced proinflammatory mediator production in fibroblast-like synoviocytesArthritis Res Ther2008; 10: R41.
- 31Djamali A, Reese S, Oberley T, et al.Heat shock protein 27 in chronic allograft nephropathy: a local stress responseTransplantation2005; 79: 1645–57.
- 32Sarto C, Valsecchi C, Magni F, et al.Expression of heat shock protein 27 in human renal cell carcinomaProteomics2004; 4: 2252–60.
- 33Gomer CJ, Ryter SW, Ferrario A, et al.Photodynamic therapy-mediated oxidative stress can induce expression of heat shock proteinsCancer Res1996; 56: 2355–60.
- 34Hanlon JG, Adams K, Rainbow AJ, et al.Induction of Hsp60 by Photofrin-mediated photodynamic therapyJ Photochem Photobiol, B2001; 64: 55–61.
- 35Feng H, Zeng Y, Whitesell L, et al.Stressed apoptotic tumor cells express heat shock proteins and elicit tumor-specific immunityBlood2001; 97: 3505–12.
- 36Flohe SB, Bruggemann J, Lendemans S, et al.Human heat shock protein 60 induces maturation of dendritic cells versus a Th1-promoting phenotypeJ Immunol2003; 170: 2340–8.
- 37Vargas-roig LM, Fanelli MA, Lopez LA, et al.Heat shock proteins and cell proliferation in human breast cancer biopsy samplesCancer Detect Prev1997; 21: 441–51.
- 38Rui Z, Jian-guo J, Yuan-peng T, et al.Use of serological proteomic methods to find biomarkers associated with breast cancerProteomics2003; 3: 433–9.
- 39Curry PM, Levy JGStress protein expression in murine tumor cells following photodynamic therapy with benzoporphyrin derivativePhotochem Photobiol1993; 58: 374–9.
- 40Jacquier-sarlin MR, Polla BSDual regulation of heat-shock transcription factor (HSF) activation and DNA-binding activity by H2O2: role of thioredoxinBiochem J1996; 1: 187–93.
- 41Stokoe D, Engel K, Campbell DG, et al.Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteinsFEBS Lett1992; 313: 307–13.
- 42Usuda J, Chiu SM, Murphy ES, et al.Domain-dependent photodamage to Bcl-2 A membrane anchorage region is needed to form the target of phthalocyanine photosensitizationJ Biol Chem2003; 278: 2021–9.
- 43Usuda J, Azizuddin K, Chiu SM, et al.Association between the photodynamic loss of Bcl-2 and the sensitivity to apoptosis caused by phthalocyanine photodynamic therapyPhotochem Photobiol2003; 78: 1–8.
- 44Usuda J, Hirata T, Ichinose S, et al.Tailor-made approach to photodynamic therapy in the treatment of cancer based on Bcl-2 photodamageInt J Oncol2008; 33: 689–96.
