Potential therapeutic efficacy of photodynamic therapy on female hormonal-dependent cancers in a hormonal simulated microenvironment.

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 17ß-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.

Comparative study of FosPeg® photodynamic effect on nasopharyngeal carcinoma cells in 2D and 3D models.

Photodynamic Therapy (PDT) offers an alternative option for the treatment of nasopharyngeal carcinoma (NPC). The utilization of 3-dimensional (3D) culture model might provide better understanding of PDT effects on NPC cells. The aim of this in vitro study was to compare PDT effect on NPC cells using 2D and 3D models. Two 3D culture models were established using liquid overlay method with agarose base (MCL) and hanging drop method (MCS). PDT was carried out using the combination of FosPeg® and 652 nm laser in 3D and conventional 2D models. The effects of 3D culture size and morphology on the uptake and distribution of sensitizer and gene expression were examined. Photocytotoxity, mode of cell death, and protein expression were compared for 2D and 3D models. Regular and irregular NPC spheroids were obtained from MCL and MCS methods, respectively. A significantly down-regulation of LMP1 mRNA were observed in MCL spheroid. The sensitizer uptake in 3D spheroids was half of 2D culture. More sensitizers were required to obtain IC50 in 3D spheroids. Apoptosis, necrosis and autophagosomes were detected in PDT treated 2D and 3D cells. Different protein expression patterns were observed in 2D and 3D models. FosPeg® PDT is effective in killing NPC cells. MCL-derived 3D spheroid model is more suitable for the evaluation of PDT killing mechanisms.

The effect of aloe-emodin-induced photodynamic activity on the apoptosis of human gastric cancer cells: A pilot study.

The aim of the present study was to explore the effect of aloe-emodin (AE)-induced photodynamic activity in human gastric cancer cells. AE was used as a photosensitizer to explore the effect of photodynamic therapy (PDT) in human gastric cancer cells (SGC-7901). An MTT assay was used to detect the effect of AE-induced PDT in optimal concentrations and illumination energy densities in human gastric cancer cells. Following AE-induced PDT, morphological changes of the cells and the rate of cell death were evaluated by TUNEL assay and flow cytometry, respectively. The expression levels of caspase-9 and caspase-3 were determined by western blot analysis. The AE and AE-induced PDT demonstrated a significant inhibitive effect on the proliferation of human gastric cancer cells in dose-dependent and energy-dependent manners. For subsequent experiments, 10 µM AE and 12.8 J/cm2 illumination energy density were used. Typical morphological changes of apoptosis were observed in the cells using a TUNEL assay 12 h subsequent to AE-induced PDT. The percentage of apoptotic cells treated with AE-induced PDT significantly increased when compared with the control group, the 10 µM AE group and the illumination group (P<0.05). Upregulation of caspase-9 and caspase-3 protein levels was also observed following AE-induced PDT. The present study revealed that 10 µM AE-induced PDT had an inhibitory effect on human gastric cancer cells, and it may induce cell apoptosis by upregulating caspase-9 and caspase-3, which indicated that the mitochondrial pathway may be involved. AE-induced PDT has the potential to be a novel therapy for the treatment of human gastric cancer. However, further investigations are required.

Tian Xian Liquid (TXL) induces apoptosis in HT-29 colon cancer cell in vitro and inhibits tumor growth in vivo.

BACKGROUND: Tian Xian Liquid (TXL) is a Chinese medicine decoction and has been used as an anticancer dietary supplement. The present study aims to investigate the effects of TXL on the apoptosis of HT-29 cells and tumor growth in vivo. METHOD: HT-29 colon cancer cells were treated with gradient dilution of TXL. The mitochondrial membrane potential was measured by JC-1 assay. The release of cytochrome c from mitochondrial and apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3, 9 were examined by Western blot analysis. HT-29 cells were implanted in nude mice to examine the effects of TXL on tumor growth. RESULT: TXL inhibited HT-29 xenografted model and showed a strong and dose-dependent inhibitory effect on the proliferation of HT-29 cells. Mitochondrial membrane potential was reduced by TXL at the concentration of 0.5% above. For Western blot analysis, an increase in Bax expression and a decrease in Bcl-2 expression were observed in TXL-treated cells. TXL treatment increased the protein level of cleaved casepase-3 and caspase-9, and the release of cytochrome c in cytoplasm was up-regulated as well. CONCLUSION: TXL significantly inhibits cell proliferation in the HT-29 cells and HT-29 xenografted model via the mitochondrial cell death pathway.

Photodynamic effect in medulloblastoma: downregulation of matrix metalloproteinases and human telomerase reverse transcriptase expressions.

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.