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Background: Photodynamic Therapy (PDT) is a clinically approved cancer treatment. Sex hormones, the key drivers for the development of female hormonal dependent cancers, might affect cancer treatment. There are seldom studies to evaluate the effect of sex hormones mimicked the menstrual cycle on the PDT mediated by prodrug 5-aminolevulinic acid (ALA) and its ester derivatives to the hormonal dependent cancers., Aims: To evaluate the efficacy of sex hormones on Hexyl-ALA-PDT in hormonal dependent cancers and the effect of the sex hormones on heme biosynthetic pathway., Methods: Cell culture system that mimicked the fluctuation of sex hormones 17β-estradiol (E2) and progesterone (PG) in the menstrual cycle was developed. Two pairs of hormonal-independent and hormonal dependent uterine sarcoma and breast cancer cell lines were used as cell models. Hexyl-ALA induced PpIX production and intracellular localization were examined. Key enzymes for PpIX synthesis were analysed. Hexyl-ALA-PDT mediated phototoxicity was evaluated., Results: The PpIX generation was increased in the hormonal-dependent cells (28-50 %) when cultured in the hormonal microenvironment with long incubation of Hexyl-ALA for 15 and 24 h compared to that cultured without hormones; whereas only slight difference in PpIX generation in their hormonal-independent counterpart. The PpIX generation was in a time-dependent manner. The CPOX, PPOX and FECH expressions were significantly enhanced by Hexyl-ALA-PDT in uterine sarcoma cells in hormonal microenvironment. Hexyl-ALA-PDT triggered significant increase of PPOX expression in breast cancer cells in hormonal microenvironment. The Hexyl-ALA-PDT phototoxicity was enhanced by 18-40 % in cells cultured in the hormonal system in a dose-dependent manner., Conclusion: The PpIX generation and the efficacy of Hexyl-ALA-PDT in both uterine sarcoma and breast cancer cells was significantly enhanced by the sex hormones via cultured in the hormonal microenvironment., (Copyright © 2024. Published by Elsevier B.V.)

Nasopharyngeal carcinoma (NPC) is one of the top ten cancers highly prevalent in Hong Kong and South China. Epstein-Barr virus (EBV) infection contributes to the tumorigenesis of NPC through the expression of different viral proteins. Among these, Latent Membrane Protein 1(LMP1) is the major oncoprotein expressed by EBV. Foscan® (Biolitec AG), m-tetrahydroxyphenylchlorin (mTHPC)-based photosensitizing drug, has been used in the photodynamic therapy (PDT) for head and neck cancers. FosPeg® (Biolitec AG) is a new formulation of mTHPC contained in PEGylated liposomes with optimized distribution properties. In this in vitro study, the potential of FosPeg®-PDT on human EBV positive NPC cell (c666-1) and EBV negative cells (HK1 and CNE2) were investigated. Effects of FosPeg®-PDT on the expression of EBV BART miRNAs (EBV miRNA BART 1-5p, BART 16, and BART 17-5p), LMP1 mRNA and proteins on c666-1 cells were also elucidated. The killing efficacy of FosPeg®-PDT on NPC cells were determined by MTT assay after LED activation. Effects of FosPeg®-PDT on the expression of LMP1 mRNA and protein were examined by real time PCR and western blot analysis. FosPeg®-PDT demonstrated its antitumor effect on c666-1 cells in a drug and light dose dependent manner. LD30, LD50 and LD70 were achieved by applying LED activation (3J/cm(2)) at 4h post incubated cells with 0.05μg/ml, 0.07μg/ml and 0.3μg/ml FosPeg®, respectively. Up-regulation of both LMP1 mRNA and protein were observed after FosPeg®-PDT in a dose dependent manner. FosPeg®-PDT exerted antitumor effect on c666-1 cells through up-regulation of LMP1 protein. Understanding the mechanism of FosPeg®-PDT may help to develop better strategies for the treatment of NPC., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aims: This study employed a doxorubicin resistant (MES-SA-Dx5) human uterine sarcoma cell line and its counterpart (MES-SA), to elucidate the efficacy of aminolevulinic acid-hexylester (hexyl-ALA) mediated PDT at molecular and transcriptional levels., Methods: Hexyl-ALA generated protoporphyrin IX in both cells were determined by molecular probes using Confocal Laser Scanning Microscopy. The hexyl-ALA-PDT induced signal transduction proteins and mode of cell death were quantitated by CASE ELISA assays and DAPI staining. The modulation of hTERT mRNA expression and telomerase activity were investigated by TaqMan real-time PCR and ELISA respectively. Hexyl-ALA-PDT mediated cell migratory effect was determined by wound-healing assay., Results: The results demonstrated that mitochondria were the major target of hexyl-ALA. At LD(30), hexyl-ALA-PDT significantly provoked an up-regulation of phosphorylated p38MAPK and JNK proteins in both cells. Hexyl-ALA-PDT down-regulated hTERT (a catalytic subunit of telomerase) mRNA expression and showed a strong correlation with diminished telomerase activity in both cells (MES-SA: r(2) = 0.9932; MES-SA-Dx5: r(2) = 0.9775). The suppression of cell migratory effect in both cells was obtained after hexyl-ALA-PDT. Further, 50% and 30% of apoptotic cells were attained at LD(50), for wild-type and drug resistant cells respectively. Unlike the wild-type, a higher PDT dose was crucial to induce apoptosis in the drug resistant cells., Conclusions: Our study provides the first evidence that p38MAPK and JNK kinases played a vital role in triggering hexyl-ALA-PDT-induced apoptosis, down-regulated hTERT mRNA expression and telomerase activity in both proposed cells. In vivo studies are worth examining for the benefit of clinical applications in drug resistant cancers and PDT development., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The aim of this study was to determine the photodynamic antimicrobial effect of hypericin on clinically isolated Staphylococcus aureus and Escherichia coli cells. Bacterial cells (10(8) cells per mL) were incubated with hypericin (0-40 μM) for 30 min and followed by light irradiation of 600-800 nm at 5-30 J cm(-2). Cell survival was determined by colony counting, cellular hypericin uptake examined by flow cytometer, and cell membrane damage examined by scanning electron microscopy and leakage assay. The effectiveness of hypericin-mediated photodynamic killing was strongly affected by cellular structure and photosensitizer uptake. The combination of hypericin and light irradiation could induce significant killing of Gram positive methicillin-sensitive and -resistant S. aureus cells (>6 log reduction), but was not effective on Gram negative E. coli cells (<0.2 log reduction). The difference was caused by different cell wall/membrane structures that directly affected cellular uptake of hypericin., (© 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.)

Gene therapy and photodynamic therapy are two kinds of important therapeutic strategies for treating malignant tumors. In order to explore the combined effects of gene therapy and PDT on tumor cells, rev-caspase-3 gene was transfected into the tumor model CNE2 cells using hypocrellin B-encapsulated nanoparticle (nano-HB) as a carrier. The transfected CNE2 cells were then irradiated by light from a LED source and the survival rate was investigated 18 h after PDT. Apoptosis was analyzed by a flow cytometer with propidium iodine (PI) staining and the active caspase-3 expression was measured using flow cytometry with phycoerythrin (PE)-conjugated anti-active caspase-3 antibody. The result from the flow cytometer showed that the level of the activated caspase-3 significantly increased up to 63.10% in the transfected CNE2 cells. The survival rate 18 h after gene transfection alone and nano-HB-mediated PDT was 96.6±2.07%, 72.6±4.15%, respectively. However, the survival rate of the transfected CNE2 cells 18 h after LED exposure significantly decreased to 50.6±5.98% under the light energy of 4 J/cm(2). Apoptotic rate 18 h after the combination of gene transfection and PDT increased up to 24.65%. Our findings demonstrated that nano-HB could significantly enhance the transfection efficiency of rev-caspase-3 gene in the CNE2 cells. LED irradiation could effectively kill the treated CNE2 cells and induce apoptosis, suggesting hypocrellin B-encapsulated nanoparticle as an efficient gene carrier and a novel photosensitizer. The combination of gene therapy and PDT using nanoparticle as a mediator can be developed for treating nasopharyngeal carcinoma., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The role of multi-drug resistance (MDR1) and its product, P-glycoprotein (P-gp) on 5-aminolevulinic acid hexyl ester (Hexyl-ALA) mediated phototoxicity was determined with human uterine sarcoma cells, MES-SA control and MDR1 expressing MES-SA-Dx5. MDR1 expression reduced intracellular levels of the Hexyl-ALA metabolite, protoporphyrin IX (PpIX) to a limited degree and could be reversed with a P-gp inhibitor, verapamil. P-gp expression also reduced Hexyl-ALA photosensitivity. More importantly, photoactivated Hexyl-ALA reduced at the mRNA and protein levels without altering housekeeping GAPDH mRNA. These findings suggest that Hexyl-ALA could be used to selectively reduce P-gp expression in overcoming resistance to chemotherapy agents such as doxorubicin and paclitaxel.

Tumor invasion and immortality are the most unfavorable drawbacks after cancer treatment. In this study, we focus on determining the photodynamic modulation of the proteolytic enzymes, matrix metalloproteinases (MMP); and a core catalytic subunit of telomerase, the human telomerase reverse transcriptase (hTERT) in medulloblastoma (MED) cell line (TE-671). Hexvix (ALA-H) mediated photodynamic therapy (PDT) demonstrated greater efficacy than 5-aminolevulinic acid (5-ALA) in terms of drug uptake and anti-proliferative effect. Both MMP-2 and hTERT expression are down-regulated quantitatively using ELISA and reverse-transcriptase-PCR (RT-PCR) respectively at post-treatment for this cell line. The MMP-9 expression remains unchanged after treatment. Further, there is a statistically significant inhibition of cell migration at 24 h post-ALA-H-PDT at LD(50) (0.01 mM, 2 J cm(-2); p < 0.001) in MED TE-671 cells. Evidently, MMP-2 and hTERT mRNA expressions can be the targets for the photodynamic intervention on tumor cell migration and immortality. Hence, PDT may be an alternate cancer regime for medulloblastoma.

Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Hong Kong and southern China. To explore a new modality of NPC treatment, 5-aminolevulinic acid (ALA) or its hexyl ester (ALA-H) mediated photodynamic therapy (PDT) was studied in vitro. The results show that NPC cells are sensitive to both ALA and ALA-H mediated PDT. However, ALA-H PDT is much more effective at cell inactivation than ALA-PDT, due to a higher efficiency of ALA-H on producing endogenous protoporphyrin (PpIX) in cells. Both apoptosis and necrosis are involved in cell death, but apoptosis plays a major role under the short time incubation of drugs. ALA and ALA-H mediated PDT not only destroy the cells directly, but also inhibit the expression of matrix metalloproteinase-2 (MMP2) in cells, a maker for tumor metastasis. The ALA-H shows promising PDT results on NPC in vitro; therefore it is worth investigating further in vivo for NPC treatment.