Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model
Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumour environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionising radiatio...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2014-12-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00356/full |
| _version_ | 1818853071839559680 |
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| author | Carole eGrasso Marie-Sophie eFabre Sarah V Collis M Leticia Castro Cameron S Field Nanette eSchleich Nanette eSchleich Melanie J McConnell Melanie J McConnell Patries M Herst Patries M Herst |
| author_facet | Carole eGrasso Marie-Sophie eFabre Sarah V Collis M Leticia Castro Cameron S Field Nanette eSchleich Nanette eSchleich Melanie J McConnell Melanie J McConnell Patries M Herst Patries M Herst |
| author_sort | Carole eGrasso |
| collection | DOAJ |
| description | Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumour environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionising radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumour, glioblastoma multiforme (GBM), is very resistant to radiation; radiosensitising GBM cells will improve survival of GBM patients. Here we demonstrate that a single fraction (6 Gy) of radiation combined with a one hour exposure to ascorbate (5 mM) sensitised murine glioma GL261cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy) of whole brain radiation combined with daily intra-peritoneal injections of ascorbate (1 mg/kg) in an intra-cranial GL261 glioma mouse model. Tumour-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain eight days after tumour implantation, a second group received daily intra-peritoneal injections of ascorbate (day 8-45 after implantation), a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumour progression, intra-peritoneal ascorbate alone had no effect on tumour progression. Tumour progression was faster in tumour-bearing mice treated with radiation and daily ascorbate than those treated with radiation alone. Histological analysis showed less necrosis in tumours treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumour micro-environment which determines whether ascorbate remains outside the cell, acting as a pro-oxidant or whether it enters the cells and acts as an anti-oxidant. |
| first_indexed | 2024-12-19T07:30:59Z |
| format | Article |
| id | doaj.art-848915498b6a4114a76bea286ab0bafc |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T07:30:59Z |
| publishDate | 2014-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-848915498b6a4114a76bea286ab0bafc2022-12-21T20:30:43ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2014-12-01410.3389/fonc.2014.00356112122Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma modelCarole eGrasso0Marie-Sophie eFabre1Sarah V Collis2M Leticia Castro3Cameron S Field4Nanette eSchleich5Nanette eSchleich6Melanie J McConnell7Melanie J McConnell8Patries M Herst9Patries M Herst10Malaghan Institute of Medical ResearchVictoria UniversityVictoria UniversityVictoria UniversityMalaghan Institute of Medical ResearchUniversity of OtagoWellington HospitalVictoria UniversityMalaghan Institute of Medical ResearchUniversity of OtagoMalaghan Institute of Medical ResearchPharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumour environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionising radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumour, glioblastoma multiforme (GBM), is very resistant to radiation; radiosensitising GBM cells will improve survival of GBM patients. Here we demonstrate that a single fraction (6 Gy) of radiation combined with a one hour exposure to ascorbate (5 mM) sensitised murine glioma GL261cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy) of whole brain radiation combined with daily intra-peritoneal injections of ascorbate (1 mg/kg) in an intra-cranial GL261 glioma mouse model. Tumour-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain eight days after tumour implantation, a second group received daily intra-peritoneal injections of ascorbate (day 8-45 after implantation), a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumour progression, intra-peritoneal ascorbate alone had no effect on tumour progression. Tumour progression was faster in tumour-bearing mice treated with radiation and daily ascorbate than those treated with radiation alone. Histological analysis showed less necrosis in tumours treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumour micro-environment which determines whether ascorbate remains outside the cell, acting as a pro-oxidant or whether it enters the cells and acts as an anti-oxidant.http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00356/fullRadiationradioprotectionPharmacological ascorbateintracranial mouse glioma modelGL261radiosensitisation |
| spellingShingle | Carole eGrasso Marie-Sophie eFabre Sarah V Collis M Leticia Castro Cameron S Field Nanette eSchleich Nanette eSchleich Melanie J McConnell Melanie J McConnell Patries M Herst Patries M Herst Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model Frontiers in Oncology Radiation radioprotection Pharmacological ascorbate intracranial mouse glioma model GL261 radiosensitisation |
| title | Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model |
| title_full | Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model |
| title_fullStr | Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model |
| title_full_unstemmed | Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model |
| title_short | Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model |
| title_sort | pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model |
| topic | Radiation radioprotection Pharmacological ascorbate intracranial mouse glioma model GL261 radiosensitisation |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00356/full |
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