Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells
Introduction: Colorectal cancer (CRC) is common, with a worldwide incidence estimated at more than 1 million cases annually. Therefore, the search for agents for CRC treatment is highly warranted. Inositol-6 phosphate (IP6) is enriched in rice bran and possesses many beneficial effects. In the prese...
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| Format: | Article |
| Language: | English |
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Termedia Publishing
2018
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| Online Access: | http://psasir.upm.edu.my/id/eprint/74694/ http://psasir.upm.edu.my/id/eprint/74694/1/Inositol-6%20phosphate%20inhibits%20the%20mTOR%20pathway.pdf |
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| author | Pandurangan, Ashok Kumar Ismail, Salmiah Mohd Esa, Norhaizan Munusamy, Murugan A. |
| author_facet | Pandurangan, Ashok Kumar Ismail, Salmiah Mohd Esa, Norhaizan Munusamy, Murugan A. |
| author_sort | Pandurangan, Ashok Kumar |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Introduction: Colorectal cancer (CRC) is common, with a worldwide incidence estimated at more than 1 million cases annually. Therefore, the search for agents for CRC treatment is highly warranted. Inositol-6 phosphate (IP6) is enriched in rice bran and possesses many beneficial effects. In the present study the effect of IP6 on autophagy-mediated death by modulating the mTOR pathway in HT-29 colon cancer cells was studied.
Material and methods: Autophagy was assessed by acridine orange (AO) staining, transmission electron microscopy, and western blotting to detect LC3-II and Beclin 1. Akt/mTOR signaling protein expression was also analyzed by western blotting. Apoptosis was analyzed by annexin V staining. Results: Incubation of cells with IP6 resulted in downregulation of the p-Akt at 3h. Along with that confocal microscopic analysis of p-AKT, IP6 administration resulted that a diminished expression of p-Akt. mTOR pathway regulates autophagy and incubation with IP6 to HT-29 cells showed decreased expression of p-70S6Kinase, 4-EBP-1 in a time-dependent manner. Inositol-6 phosphate (10 μg/ml, 24 and 48 h) induced autophagic vesicles, as confirmed by AO staining and transmission electron microscopy. We also found increased expression of LC3-II and Beclin 1 in a time-dependent manner after incubation with IP6. Furthermore, IP6 induced apoptosis, as revealed by annexin V staining. Conclusions: Our results clearly indicate that IP6 induces autophagy by inhibiting the Akt/mTOR pathway. |
| first_indexed | 2025-11-15T11:59:10Z |
| format | Article |
| id | upm-74694 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T11:59:10Z |
| publishDate | 2018 |
| publisher | Termedia Publishing |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-746942019-10-15T03:47:38Z http://psasir.upm.edu.my/id/eprint/74694/ Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells Pandurangan, Ashok Kumar Ismail, Salmiah Mohd Esa, Norhaizan Munusamy, Murugan A. Introduction: Colorectal cancer (CRC) is common, with a worldwide incidence estimated at more than 1 million cases annually. Therefore, the search for agents for CRC treatment is highly warranted. Inositol-6 phosphate (IP6) is enriched in rice bran and possesses many beneficial effects. In the present study the effect of IP6 on autophagy-mediated death by modulating the mTOR pathway in HT-29 colon cancer cells was studied. Material and methods: Autophagy was assessed by acridine orange (AO) staining, transmission electron microscopy, and western blotting to detect LC3-II and Beclin 1. Akt/mTOR signaling protein expression was also analyzed by western blotting. Apoptosis was analyzed by annexin V staining. Results: Incubation of cells with IP6 resulted in downregulation of the p-Akt at 3h. Along with that confocal microscopic analysis of p-AKT, IP6 administration resulted that a diminished expression of p-Akt. mTOR pathway regulates autophagy and incubation with IP6 to HT-29 cells showed decreased expression of p-70S6Kinase, 4-EBP-1 in a time-dependent manner. Inositol-6 phosphate (10 μg/ml, 24 and 48 h) induced autophagic vesicles, as confirmed by AO staining and transmission electron microscopy. We also found increased expression of LC3-II and Beclin 1 in a time-dependent manner after incubation with IP6. Furthermore, IP6 induced apoptosis, as revealed by annexin V staining. Conclusions: Our results clearly indicate that IP6 induces autophagy by inhibiting the Akt/mTOR pathway. Termedia Publishing 2018-10 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/74694/1/Inositol-6%20phosphate%20inhibits%20the%20mTOR%20pathway.pdf Pandurangan, Ashok Kumar and Ismail, Salmiah and Mohd Esa, Norhaizan and Munusamy, Murugan A. (2018) Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells. Archives of Medical Sciences, 14 (6). 1281 - 1288. ISSN 1734-1922; ESSN: 1896-9151 https://www.termedia.pl/Inositol-6-phosphate-inhibits-the-mTOR-pathway-and-induces-autophagy-mediated-death-in-HT-29-colon-cancer-cells,19,33250,0,1.html 10.5114/aoms.2018.76935 |
| spellingShingle | Pandurangan, Ashok Kumar Ismail, Salmiah Mohd Esa, Norhaizan Munusamy, Murugan A. Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells |
| title | Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells |
| title_full | Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells |
| title_fullStr | Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells |
| title_full_unstemmed | Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells |
| title_short | Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells |
| title_sort | inositol-6 phosphate inhibits the mtor pathway and induces autophagy-mediated death in ht-29 colon cancer cells |
| url | http://psasir.upm.edu.my/id/eprint/74694/ http://psasir.upm.edu.my/id/eprint/74694/ http://psasir.upm.edu.my/id/eprint/74694/ http://psasir.upm.edu.my/id/eprint/74694/1/Inositol-6%20phosphate%20inhibits%20the%20mTOR%20pathway.pdf |