Abstract
Background:
Photodynamic Therapy (PDT) is an alternative treatment modality approved by FDA for various cancers. Basically, ALA-based PDT efficacy is highly dependent on the accumulation of protoporphyrin IX (PpIX) generated via the disrupted heme biosynthetic pathway in cancer cells. Hormones interplay a vital role in cancer physiology, carcinogenesis, and treatment modality, but seldom studies integrated the differential effects of hormones in microenvironment modulating the ALA-based PDT efficacy. Besides, the traditional cell culture model only with single hormonal dose limits the real hormonal effects of cancer cells that grow in normal physiological microenvironment. Hence, this study aimed to study the differential effects of sex hormones to ALA-based-PDT efficacy via the regulation of three rate-limiting enzymes in heme biosynthetic pathway on breast cancer cells using the newly established culture model mimicking the hormonal changes in normal human menstrual cycle.
Methods:
The MCF7 cells were cultured by the system mimicking the changes of 17β-estradiol and progesterone levels during menstrual cycle. The cells were further treated by Hexyl-ALA-PDT and the expression levels of the three rate-determining enzymes in heme pathway namely ferrochelatase (FECH), Protoporphyrinogen Oxidase (PPOX), and Coproporphyrinogen Oxidase (CPOX) were quantified by flow cytometry. Cells treated without hormones and with respect to the inhibitor of each enzyme were included as controls.
Results:
At LD30 and 4hrs post-Hexyl-ALA-PDT, FECH expression was significantly increased in 2-fold in the cells grow in the system compared to those without hormones and with deferoxamine (DFX - an FECH inhibitor). However, CPOX and PPOX expression remained unchanged. The results demonstrated the hormonal changes in microenvironment enhanced Hexyl-ALA-PDT efficacy via the activation of FECH in heme pathway.
Conclusions:
This study showed Hexyl-ALA-PDT efficacy in breast cancer cells significantly enhanced by the hormonal microenvironment. Further in-depth mechanistic studies to elucidate sex hormones modulating Hexyl-ALA-PDT efficacy are deserved to be explored.
Acknowledgement:
Hexyl-ALA was kindly provided by Photocure ASA. This study was fully supported by a grant from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region, China (Project no.: UGC/FDS17/M06/19).
Photodynamic Therapy (PDT) is an alternative treatment modality approved by FDA for various cancers. Basically, ALA-based PDT efficacy is highly dependent on the accumulation of protoporphyrin IX (PpIX) generated via the disrupted heme biosynthetic pathway in cancer cells. Hormones interplay a vital role in cancer physiology, carcinogenesis, and treatment modality, but seldom studies integrated the differential effects of hormones in microenvironment modulating the ALA-based PDT efficacy. Besides, the traditional cell culture model only with single hormonal dose limits the real hormonal effects of cancer cells that grow in normal physiological microenvironment. Hence, this study aimed to study the differential effects of sex hormones to ALA-based-PDT efficacy via the regulation of three rate-limiting enzymes in heme biosynthetic pathway on breast cancer cells using the newly established culture model mimicking the hormonal changes in normal human menstrual cycle.
Methods:
The MCF7 cells were cultured by the system mimicking the changes of 17β-estradiol and progesterone levels during menstrual cycle. The cells were further treated by Hexyl-ALA-PDT and the expression levels of the three rate-determining enzymes in heme pathway namely ferrochelatase (FECH), Protoporphyrinogen Oxidase (PPOX), and Coproporphyrinogen Oxidase (CPOX) were quantified by flow cytometry. Cells treated without hormones and with respect to the inhibitor of each enzyme were included as controls.
Results:
At LD30 and 4hrs post-Hexyl-ALA-PDT, FECH expression was significantly increased in 2-fold in the cells grow in the system compared to those without hormones and with deferoxamine (DFX - an FECH inhibitor). However, CPOX and PPOX expression remained unchanged. The results demonstrated the hormonal changes in microenvironment enhanced Hexyl-ALA-PDT efficacy via the activation of FECH in heme pathway.
Conclusions:
This study showed Hexyl-ALA-PDT efficacy in breast cancer cells significantly enhanced by the hormonal microenvironment. Further in-depth mechanistic studies to elucidate sex hormones modulating Hexyl-ALA-PDT efficacy are deserved to be explored.
Acknowledgement:
Hexyl-ALA was kindly provided by Photocure ASA. This study was fully supported by a grant from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region, China (Project no.: UGC/FDS17/M06/19).
Original language | English |
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Publication status | Published - 16 Jun 2022 |
Event | 2nd International Congress of Asian Oncology Society & 48th Annual Meeting of Korean Cancer Association - Lotte Hotel, Seoul, Korea, Republic of Duration: 16 Jun 2022 → 18 Jun 2022 https://www.aos2022.com/html/index.html (Link to conference website) |
Conference
Conference | 2nd International Congress of Asian Oncology Society & 48th Annual Meeting of Korean Cancer Association |
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Abbreviated title | AOS 2022 |
Country/Territory | Korea, Republic of |
City | Seoul |
Period | 16/06/22 → 18/06/22 |
Internet address |
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