Simultaneous Assessment of the Efficacy and Toxicity of Marine Mollusc–Derived Brominated Indoles in an In Vivo Model for Early Stage Colon Cancer
The acute apoptotic response to genotoxic carcinogens animal model has been extensively used to assess the ability of drugs and natural products like dietary components to promote apoptosis in the colon and protect against colorectal cancer (CRC). This work aimed to use this model to identify the ma...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2018-06-01
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| Series: | Integrative Cancer Therapies |
| Online Access: | https://doi.org/10.1177/1534735417699880 |
| _version_ | 1818576053843525632 |
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| author | Babak Esmaeelian PhD Kirsten Benkendorff PhD Richard K. Le Leu PhD Catherine A. Abbott PhD |
| author_facet | Babak Esmaeelian PhD Kirsten Benkendorff PhD Richard K. Le Leu PhD Catherine A. Abbott PhD |
| author_sort | Babak Esmaeelian PhD |
| collection | DOAJ |
| description | The acute apoptotic response to genotoxic carcinogens animal model has been extensively used to assess the ability of drugs and natural products like dietary components to promote apoptosis in the colon and protect against colorectal cancer (CRC). This work aimed to use this model to identify the main chemopreventative agent in extracts from an Australian mollusc Dicathais orbita , while simultaneously providing information on their potential in vivo toxicity. After 2 weeks of daily oral gavage with bioactive extracts and purified brominated indoles, mice were injected with the chemical carcinogen azoxymethane (AOM; 10 mg/kg) and then killed 6 hours later. Efficacy was evaluated using immunohistochemical and hematoxylin staining, and toxicity was assessed via hematology, blood biochemistry, and liver histopathology. Comparison of saline- and AOM-injected controls revealed that potential toxic side effects can be interpreted from blood biochemistry and hematology using this short-term model, although AOM negatively affected the ability to detect histopathological effects in the liver. Purified 6-bromoisatin was identified as the main cancer preventive agent in the Muricidae extract, significantly enhancing apoptosis and reducing cell proliferation in the colonic crypts at 0.05 mg/g. There was no evidence of liver toxicity associated with 6-bromoisatin, whereas 0.1 mg/g of the brominated indole tyrindoleninone led to elevated aspartate aminotransferase levels and a reduction in red blood cells. As tyrindoleninone is converted to 6-bromoisatin by oxidation, this information will assist in the optimization and quality control of a chemopreventative nutraceutical from Muricidae. In conclusion, preliminary data on in vivo safety can be simultaneously collected when testing the efficacy of new natural products, such as 6-bromoisatin from Muricidae molluscs for early stage prevention of colon cancer. |
| first_indexed | 2024-12-15T00:49:03Z |
| format | Article |
| id | doaj.art-beaecaa95bab45fba4a7d2319e46a1c3 |
| institution | Directory Open Access Journal |
| issn | 1534-7354 1552-695X |
| language | English |
| last_indexed | 2024-12-15T00:49:03Z |
| publishDate | 2018-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Integrative Cancer Therapies |
| spelling | doaj.art-beaecaa95bab45fba4a7d2319e46a1c32022-12-21T22:41:27ZengSAGE PublishingIntegrative Cancer Therapies1534-73541552-695X2018-06-011710.1177/1534735417699880Simultaneous Assessment of the Efficacy and Toxicity of Marine Mollusc–Derived Brominated Indoles in an In Vivo Model for Early Stage Colon CancerBabak Esmaeelian PhD0Kirsten Benkendorff PhD1Richard K. Le Leu PhD2Catherine A. Abbott PhD3School of Biological Sciences, Flinders University, Adelaide, South Australia, AustraliaMarine Ecology Research Centre, School of Environment, Science and Engineering, Southern Cross University, Lismore, New South Wales, AustraliaFlinders Centre for Innovation in Cancer, Flinders University, Adelaide, South Australia, AustraliaFlinders Centre for Innovation in Cancer, Flinders University, Adelaide, South Australia, AustraliaThe acute apoptotic response to genotoxic carcinogens animal model has been extensively used to assess the ability of drugs and natural products like dietary components to promote apoptosis in the colon and protect against colorectal cancer (CRC). This work aimed to use this model to identify the main chemopreventative agent in extracts from an Australian mollusc Dicathais orbita , while simultaneously providing information on their potential in vivo toxicity. After 2 weeks of daily oral gavage with bioactive extracts and purified brominated indoles, mice were injected with the chemical carcinogen azoxymethane (AOM; 10 mg/kg) and then killed 6 hours later. Efficacy was evaluated using immunohistochemical and hematoxylin staining, and toxicity was assessed via hematology, blood biochemistry, and liver histopathology. Comparison of saline- and AOM-injected controls revealed that potential toxic side effects can be interpreted from blood biochemistry and hematology using this short-term model, although AOM negatively affected the ability to detect histopathological effects in the liver. Purified 6-bromoisatin was identified as the main cancer preventive agent in the Muricidae extract, significantly enhancing apoptosis and reducing cell proliferation in the colonic crypts at 0.05 mg/g. There was no evidence of liver toxicity associated with 6-bromoisatin, whereas 0.1 mg/g of the brominated indole tyrindoleninone led to elevated aspartate aminotransferase levels and a reduction in red blood cells. As tyrindoleninone is converted to 6-bromoisatin by oxidation, this information will assist in the optimization and quality control of a chemopreventative nutraceutical from Muricidae. In conclusion, preliminary data on in vivo safety can be simultaneously collected when testing the efficacy of new natural products, such as 6-bromoisatin from Muricidae molluscs for early stage prevention of colon cancer.https://doi.org/10.1177/1534735417699880 |
| spellingShingle | Babak Esmaeelian PhD Kirsten Benkendorff PhD Richard K. Le Leu PhD Catherine A. Abbott PhD Simultaneous Assessment of the Efficacy and Toxicity of Marine Mollusc–Derived Brominated Indoles in an In Vivo Model for Early Stage Colon Cancer Integrative Cancer Therapies |
| title | Simultaneous Assessment of the Efficacy and Toxicity of Marine Mollusc–Derived Brominated Indoles in an In Vivo Model for Early Stage Colon Cancer |
| title_full | Simultaneous Assessment of the Efficacy and Toxicity of Marine Mollusc–Derived Brominated Indoles in an In Vivo Model for Early Stage Colon Cancer |
| title_fullStr | Simultaneous Assessment of the Efficacy and Toxicity of Marine Mollusc–Derived Brominated Indoles in an In Vivo Model for Early Stage Colon Cancer |
| title_full_unstemmed | Simultaneous Assessment of the Efficacy and Toxicity of Marine Mollusc–Derived Brominated Indoles in an In Vivo Model for Early Stage Colon Cancer |
| title_short | Simultaneous Assessment of the Efficacy and Toxicity of Marine Mollusc–Derived Brominated Indoles in an In Vivo Model for Early Stage Colon Cancer |
| title_sort | simultaneous assessment of the efficacy and toxicity of marine mollusc derived brominated indoles in an in vivo model for early stage colon cancer |
| url | https://doi.org/10.1177/1534735417699880 |
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