Effects of Supplemental Drugs on Hexaminolevulinate (HAL)-Induced PpIX Fluorescence in Bladder Cancer Cell Suspensions

Seven different inhibitors of the heme metabolic pathway were applied in combination with HAL to study the formation of PpIX in bladder cancer HT1197 and normal fibroblast HFFF2 cells ex vivo, specifically with the aim to increase the fluorescence contrast between cancer and non-cancer cells. The mR...

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Main Authors: Kit Man Chan, Krasimir Vasilev, Melanie MacGregor
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/14/7631
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author Kit Man Chan
Krasimir Vasilev
Melanie MacGregor
author_facet Kit Man Chan
Krasimir Vasilev
Melanie MacGregor
author_sort Kit Man Chan
collection DOAJ
description Seven different inhibitors of the heme metabolic pathway were applied in combination with HAL to study the formation of PpIX in bladder cancer HT1197 and normal fibroblast HFFF2 cells ex vivo, specifically with the aim to increase the fluorescence contrast between cancer and non-cancer cells. The mRNA expression of enzymes involved in the heme biosynthesis pathway were measured via PCR following incubation with the drugs in order to link the fluorescence levels and metabolic activity. The exogenous administration of HAL does lead to cancer-specific PpIX accumulation. However, the contrast between cancer and normal cells in suspension was not enhanced by the enzyme inhibitors and iron-chelating agents tested, nor did the mRNA expression necessarily correlate with the fluorescence intensity. The results indicate that a difference in the metabolic activity of cells in suspension may limit the applicability of exogenous enzyme inhibitor administration as a mean to improve the fluorescence-based detection of cancer cells shed in body fluids.
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spelling doaj.art-f0e1cf6d092f4688974f59536e62624c2023-12-03T15:09:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314763110.3390/ijms23147631Effects of Supplemental Drugs on Hexaminolevulinate (HAL)-Induced PpIX Fluorescence in Bladder Cancer Cell SuspensionsKit Man Chan0Krasimir Vasilev1Melanie MacGregor2UniSA STEM, University of South Australia, Adelaide, SA 5095, AustraliaCollege of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, AustraliaFlinders Institute for Nanoscale Science & Technology, College of Science and Engineering, Flinders University, Bedford Park, SA 5042, AustraliaSeven different inhibitors of the heme metabolic pathway were applied in combination with HAL to study the formation of PpIX in bladder cancer HT1197 and normal fibroblast HFFF2 cells ex vivo, specifically with the aim to increase the fluorescence contrast between cancer and non-cancer cells. The mRNA expression of enzymes involved in the heme biosynthesis pathway were measured via PCR following incubation with the drugs in order to link the fluorescence levels and metabolic activity. The exogenous administration of HAL does lead to cancer-specific PpIX accumulation. However, the contrast between cancer and normal cells in suspension was not enhanced by the enzyme inhibitors and iron-chelating agents tested, nor did the mRNA expression necessarily correlate with the fluorescence intensity. The results indicate that a difference in the metabolic activity of cells in suspension may limit the applicability of exogenous enzyme inhibitor administration as a mean to improve the fluorescence-based detection of cancer cells shed in body fluids.https://www.mdpi.com/1422-0067/23/14/7631hexaminolevulinateprotoporphyrin IXbladder cancerfluorescencePPOXFECH
spellingShingle Kit Man Chan
Krasimir Vasilev
Melanie MacGregor
Effects of Supplemental Drugs on Hexaminolevulinate (HAL)-Induced PpIX Fluorescence in Bladder Cancer Cell Suspensions
International Journal of Molecular Sciences
hexaminolevulinate
protoporphyrin IX
bladder cancer
fluorescence
PPOX
FECH
title Effects of Supplemental Drugs on Hexaminolevulinate (HAL)-Induced PpIX Fluorescence in Bladder Cancer Cell Suspensions
title_full Effects of Supplemental Drugs on Hexaminolevulinate (HAL)-Induced PpIX Fluorescence in Bladder Cancer Cell Suspensions
title_fullStr Effects of Supplemental Drugs on Hexaminolevulinate (HAL)-Induced PpIX Fluorescence in Bladder Cancer Cell Suspensions
title_full_unstemmed Effects of Supplemental Drugs on Hexaminolevulinate (HAL)-Induced PpIX Fluorescence in Bladder Cancer Cell Suspensions
title_short Effects of Supplemental Drugs on Hexaminolevulinate (HAL)-Induced PpIX Fluorescence in Bladder Cancer Cell Suspensions
title_sort effects of supplemental drugs on hexaminolevulinate hal induced ppix fluorescence in bladder cancer cell suspensions
topic hexaminolevulinate
protoporphyrin IX
bladder cancer
fluorescence
PPOX
FECH
url https://www.mdpi.com/1422-0067/23/14/7631
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AT melaniemacgregor effectsofsupplementaldrugsonhexaminolevulinatehalinducedppixfluorescenceinbladdercancercellsuspensions