Apoptosis and expression of cytokines triggered by pyropheophorbide-a methyl ester-mediated photodynamic therapy in nasopharyngeal carcinoma cells.

The photodynamic properties of pyropheophorbide-a methyl ester (MPPa), a semi-synthetic photosensitizer derived from chlorophyll a, were evaluated in a human nasopharyngeal carcinoma HONE-1 cell line. MPPa was non-toxic to the HONE-1. At the concentrations of 0.5-2μM, MPPa-mediated a drug dose-dependent photocytotoxicity in the HONE-1 cells. Confocal microscopy revealed a subcellular localization of MPPa in mitochondria and the Golgi apparatus. MPPa PDT-induced apoptosis was associated with the collapse of mitochondrial membrane potential, release of cytochrome c, the up-regulation of endoplasmic reticulum (ER) stress proteins (calnexin, Grp 94 and Grp78), and the activation of caspases-3 and -9. The photocytotoxicity was reduced by the corresponding specific caspase inhibitors. MPPa PDT-treated HONE-1 cells also up-regulated the gene expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and beta-chemokines (MIP-1β, MPIF-1, and MPIF-2). These results suggest that the MPPa may be developed as a chlorophyll-based photosensitizer for the treatment of nasopharyngeal carcinoma.

[1]  Barbara W Henderson,et al.  Photodynamic therapy: a means to enhanced drug delivery to tumors. , 2003, Cancer research.

[2]  J. Piette,et al.  Downregulation of ICAM-1 and VCAM-1 expression in endothelial cells treated by photodynamic therapy , 2004, Oncogene.

[3]  K. Yao,et al.  Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Stanley B. Brown,et al.  An overview of synthetic approaches to porphyrin, phthalocyanine, and phenothiazine photosensitizers for photodynamic therapy. , 2006, Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer.

[5]  M. Olivo,et al.  Hypericin-mediated photodynamic therapy elicits differential interleukin-6 response in nasopharyngeal cancer , 2006 .

[6]  P. Agostinis,et al.  Cell death and growth arrest in response to photodynamic therapy with membrane-bound photosensitizers. , 2003, Biochemical pharmacology.

[7]  Albert Wingnang Leung,et al.  Photodynamic effects of pyropheophorbide-a methyl ester in nasopharyngeal carcinoma cells. , 2006, Medical science monitor : international medical journal of experimental and clinical research.

[8]  T. Dougherty,et al.  Photodynamic therapy for sarcoma pulmonary metastases: a preclinical toxicity study. , 2003, Anticancer research.

[9]  C. Tsai,et al.  Profile of cytokine expression in nasopharyngeal carcinomas: a distinct expression of interleukin 1 in tumor and CD4+ T cells. , 1999, Cancer research.

[10]  J. Piette,et al.  Pyropheophorbide-a Methyl Ester-mediated Photosensitization Activates Transcription Factor NF-κB through the Interleukin-1 Receptor-dependent Signaling Pathway* , 1999, The Journal of Biological Chemistry.

[11]  B. Nardelli,et al.  Dendritic cells and MPIF‐1: chemotactic activity and inhibition of endogenous chemokine production by IFN‐γ and CD40 ligation , 1999, Journal of leukocyte biology.

[12]  M. Olivo,et al.  Endogenous expression of interleukin-8 and interleukin-10 in nasopharyngeal carcinoma cells and the effect of photodynamic therapy. , 2002, International journal of molecular medicine.

[13]  B. Nardelli,et al.  Analysis of eosinophils and myeloid progenitor responses to modified forms of MPIF-2. , 2001, Cytokine.

[14]  Chi K. Chang,et al.  Photodynamic activities of sulfonamide derivatives of porphycene on nasopharyngeal carcinoma cells. , 2003, Journal of biomedical science.

[15]  R. Wong,et al.  Inhibition of RANTES expression by indirubin in influenza virus-infected human bronchial epithelial cells. , 2004, Biochemical pharmacology.

[16]  H. Sarau,et al.  Cloning and functional characterization of a novel human CC chemokine that binds to the CCR3 receptor and activates human eosinophils , 1997, Journal of leukocyte biology.

[17]  Kevin M. Smith,et al.  Alkyl Ether Analogs of Chlorophyll‐a Derivatives: Part 1. Synthesis, Photophysical Properties and Photodynamic Efficacy , 1996, Photochemistry and photobiology.

[18]  P. Hynninen,et al.  Research advances in the use of tetrapyrrolic photosensitizers for photodynamic therapy. , 2004, Journal of photochemistry and photobiology. B, Biology.

[19]  A. Scherz,et al.  Combined hyperthermia and chlorophyll-based photodynamic therapy: tumour growth and metabolic microenvironment , 2003, British Journal of Cancer.

[20]  R. Gentz,et al.  Molecular and Functional Characterization of  Two Novel Human C-C Chemokines as Inhibitors of  Two Distinct Classes of Myeloid Progenitors , 1997, The Journal of experimental medicine.

[21]  Michael R Hamblin,et al.  Photodynamic therapy and anti-tumour immunity , 2006, Nature Reviews Cancer.

[22]  Won-Young Lee,et al.  Silkworm-pheophorbide alpha mediated photodynamic therapy against B16F10 pigmented melanoma. , 2004, Journal of photochemistry and photobiology. B, Biology.

[23]  B W Henderson,et al.  Role of cytokines in photodynamic therapy-induced local and systemic inflammation , 2003, British Journal of Cancer.

[24]  S. Jee,et al.  Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency , 2001, Oncogene.

[25]  L. Villeneuve.  Ex vivo photodynamic purging in chronic myelogenous leukaemia and other neoplasias with rhodamine derivatives , 1999, Biotechnology and applied biochemistry.

[26]  Nancy L Oleinick,et al.  The role of apoptosis in response to photodynamic therapy: what, where, why, and how , 2002, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[27]  M. Baggiolini,et al.  CKβ8, a novel CC chemokine that predominantly acts on monocytes , 1997 .

[28]  W. Leung,et al.  Photodynamic Therapy with Pyropheophorbide-a Methyl Ester in Human Lung Carcinoma Cancer Cell: Efficacy, Localization and Apoptosis¶ , 2002 .

[29]  B. Kwon,et al.  Characterization of CKβ8 and CKβ8-1: Two Alternatively Spliced Forms of Human β-Chemokine, Chemoattractants for Neutrophils, Monocytes, and Lymphocytes, and Potent Agonists at CC Chemokine Receptor 1 , 1998 .

[30]  T. Vogl,et al.  A multicenter Phase I safety study of intratumoral photoactivation of talaporfin sodium in patients with refractory solid tumors , 2003, Cancer.

[31]  M. Ahn,et al.  Photoactivation of pheophorbide a induces a mitochondrial-mediated apoptosis in Jurkat leukaemia cells. , 2004, Journal of photochemistry and photobiology. B, Biology.

[32]  M. Lung,et al.  Involvement of both endoplasmic reticulum and mitochondria in photokilling of nasopharyngeal carcinoma cells by the photosensitizer Zn-BC-AM. , 2004, Biochemical pharmacology.

[33]  J. Piette,et al.  Mechanism of colon cancer cell apoptosis mediated by pyropheophorbide-a methylester photosensitization , 2001, Oncogene.

[34]  J. Usuda,et al.  Increased cytotoxic effects of photodynamic therapy in IL‐6 gene transfected cells via enhanced apoptosis , 2001, International journal of cancer.

[35]  Stanley B. Brown,et al.  The present and future role of photodynamic therapy in cancer treatment. , 2004, The Lancet. Oncology.

[36]  M. Olivo,et al.  Mechanisms of action of phenanthroperylenequinones in photodynamic therapy (review). , 2003, International journal of oncology.