6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model
Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectrosc...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2013-12-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1660-3397/12/1/17 |
| _version_ | 1811278774009856000 |
|---|---|
| author | Babak Esmaeelian Catherine A. Abbott Richard K. Le Leu Kirsten Benkendorff |
| author_facet | Babak Esmaeelian Catherine A. Abbott Richard K. Le Leu Kirsten Benkendorff |
| author_sort | Babak Esmaeelian |
| collection | DOAJ |
| description | Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC50 223 μM (0.05 mg/mL) and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g) was found to significantly enhance the apoptotic index (p ≤ 0.001) and reduced cell proliferation (p ≤ 0.01) in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer. |
| first_indexed | 2024-04-13T00:43:01Z |
| format | Article |
| id | doaj.art-2e8b99b8f1e7428487eaa30a3a8703b5 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-13T00:43:01Z |
| publishDate | 2013-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-2e8b99b8f1e7428487eaa30a3a8703b52022-12-22T03:10:06ZengMDPI AGMarine Drugs1660-33972013-12-01121173510.3390/md12010017md120100176-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent ModelBabak Esmaeelian0Catherine A. Abbott1Richard K. Le Leu2Kirsten Benkendorff3School of Biological Sciences, Flinders University, GPO Box 2100, Adelaide 5001, AustraliaSchool of Biological Sciences, Flinders University, GPO Box 2100, Adelaide 5001, AustraliaFlinders Centre for Innovation in Cancer, Flinders University, GPO Box 2100, Adelaide 5001, AustraliaMarine Ecology Research Centre, School of Environment, Science and Engineering, Southern Cross University, GPO Box 157, Lismore, NSW 2480, AustraliaMuricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC50 223 μM (0.05 mg/mL) and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g) was found to significantly enhance the apoptotic index (p ≤ 0.001) and reduced cell proliferation (p ≤ 0.01) in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer.http://www.mdpi.com/1660-3397/12/1/17apoptosisazoxymethanebioactive natural product colorectal cancerisatin in vivo modelmarine mollusc |
| spellingShingle | Babak Esmaeelian Catherine A. Abbott Richard K. Le Leu Kirsten Benkendorff 6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model Marine Drugs apoptosis azoxymethane bioactive natural product colorectal cancer isatin in vivo model marine mollusc |
| title | 6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model |
| title_full | 6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model |
| title_fullStr | 6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model |
| title_full_unstemmed | 6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model |
| title_short | 6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model |
| title_sort | 6 bromoisatin found in muricid mollusc extracts inhibits colon cancer cell proliferation and induces apoptosis preventing early stage tumor formation in a colorectal cancer rodent model |
| topic | apoptosis azoxymethane bioactive natural product colorectal cancer isatin in vivo model marine mollusc |
| url | http://www.mdpi.com/1660-3397/12/1/17 |
| work_keys_str_mv | AT babakesmaeelian 6bromoisatinfoundinmuricidmolluscextractsinhibitscoloncancercellproliferationandinducesapoptosispreventingearlystagetumorformationinacolorectalcancerrodentmodel AT catherineaabbott 6bromoisatinfoundinmuricidmolluscextractsinhibitscoloncancercellproliferationandinducesapoptosispreventingearlystagetumorformationinacolorectalcancerrodentmodel AT richardkleleu 6bromoisatinfoundinmuricidmolluscextractsinhibitscoloncancercellproliferationandinducesapoptosispreventingearlystagetumorformationinacolorectalcancerrodentmodel AT kirstenbenkendorff 6bromoisatinfoundinmuricidmolluscextractsinhibitscoloncancercellproliferationandinducesapoptosispreventingearlystagetumorformationinacolorectalcancerrodentmodel |