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...

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Main Authors: Ellie Shihng-meir Chu, Ricky Wing-kei Wu, Zheng Huang
Format: Article
Language:English
Published: Elsevier 2024-02-01
Series:Photodiagnosis and Photodynamic Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S1572100024000371
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author Ellie Shihng-meir Chu
Ricky Wing-kei Wu
Zheng Huang
author_facet Ellie Shihng-meir Chu
Ricky Wing-kei Wu
Zheng Huang
author_sort Ellie Shihng-meir Chu
collection DOAJ
description 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.
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spelling doaj-art-799eeb98186c4b8683c0e759e883990c2024-12-11T05:55:41ZengElsevierPhotodiagnosis and Photodynamic Therapy1572-10002024-02-0145103998Potential therapeutic efficacy of photodynamic therapy on female hormonal-dependent cancers in a hormonal simulated microenvironmentEllie Shihng-meir Chu0Ricky Wing-kei Wu1Zheng Huang2School of Medical & Health Sciences, Tung Wah College, Hong Kong SAR, China; Corresponding author.Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, Scotland, UKMOE Key Laboratory of Photonics Science and Technology for Medicine, Fujian Normal University, Fuzhou, ChinaBackground: 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.http://www.sciencedirect.com/science/article/pii/S1572100024000371Photodynamic therapyHexyl-ALAHormonal microenvironmentHeme pathwaySex hormones
spellingShingle Ellie Shihng-meir Chu
Ricky Wing-kei Wu
Zheng Huang
Potential therapeutic efficacy of photodynamic therapy on female hormonal-dependent cancers in a hormonal simulated microenvironment
Photodiagnosis and Photodynamic Therapy
Photodynamic therapy
Hexyl-ALA
Hormonal microenvironment
Heme pathway
Sex hormones
title Potential therapeutic efficacy of photodynamic therapy on female hormonal-dependent cancers in a hormonal simulated microenvironment
title_full Potential therapeutic efficacy of photodynamic therapy on female hormonal-dependent cancers in a hormonal simulated microenvironment
title_fullStr Potential therapeutic efficacy of photodynamic therapy on female hormonal-dependent cancers in a hormonal simulated microenvironment
title_full_unstemmed Potential therapeutic efficacy of photodynamic therapy on female hormonal-dependent cancers in a hormonal simulated microenvironment
title_short Potential therapeutic efficacy of photodynamic therapy on female hormonal-dependent cancers in a hormonal simulated microenvironment
title_sort potential therapeutic efficacy of photodynamic therapy on female hormonal dependent cancers in a hormonal simulated microenvironment
topic Photodynamic therapy
Hexyl-ALA
Hormonal microenvironment
Heme pathway
Sex hormones
url http://www.sciencedirect.com/science/article/pii/S1572100024000371
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AT rickywingkeiwu potentialtherapeuticefficacyofphotodynamictherapyonfemalehormonaldependentcancersinahormonalsimulatedmicroenvironment
AT zhenghuang potentialtherapeuticefficacyofphotodynamictherapyonfemalehormonaldependentcancersinahormonalsimulatedmicroenvironment