Cargando…
Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways
BACKGROUND: Pancreatic cancer causes tremendous mortality across the globe mainly due to late diagnosis and unavailability of efficient chemotheruptic agents. In the current study the anticancer potential of a plant derived alkaloid, Mahanimbine, was examined against a panel of pancreatic cancer cel...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178883/ https://www.ncbi.nlm.nih.gov/pubmed/30273298 http://dx.doi.org/10.12659/MSM.911013 |
_version_ | 1783362003301040128 |
---|---|
author | Pei, Chenlin He, Qun Liang, Shuai Gong, Xuejun |
author_facet | Pei, Chenlin He, Qun Liang, Shuai Gong, Xuejun |
author_sort | Pei, Chenlin |
collection | PubMed |
description | BACKGROUND: Pancreatic cancer causes tremendous mortality across the globe mainly due to late diagnosis and unavailability of efficient chemotheruptic agents. In the current study the anticancer potential of a plant derived alkaloid, Mahanimbine, was examined against a panel of pancreatic cancer cells. MATERIAL/METHODS: The cell proliferation was determined by MTT assay. Annexin V/PI and DAPI staining were performed to detect apoptosis. Cell cycle distribution was investigated by flow cytometery. Cell migration was detected by wound healing assay and protein expression was checked by western blotting. RESULTS: The results revealed that Mahanimbine could inhibit the proliferation of the all the pancreatic cancer cells with lower cytoxicity against the normal cells. The IC(50) ranged from 3.5 to 64 μM against the pancreatic cancer cell lines. The lowest IC(50) of 3.5 μM was observed tor the Capan-2 and SW119 pancreatic cancer cell lines. The anticancer activity of Mahanimbine against the Capan-2 and SW119 cells was found to be due to G(0)/G(1) cell cycle arrest and induction of apoptosis. Mahanimbine prompted apoptosis was also associated with decline in Bcl-2 and enhancement of the Bax expression. Further, it was observed that Mahanimbine could inhibit the AKT/mTOR and STAT3 signalling pathways in the Capan-2 and SW119 pancreatic cancer cells. The effects of the Mahanimbine were also examined on the migration of the Capan-2 and SW119 pancreatic cancer cells. It was found that Mahanimbine could inhibit the motility and migration of both the pancreatic cancer cell lines. CONCLUSIONS: We found that Mahanimbine inhibits the proliferation of pancreatic cancer cells and as such Mahanimbine may prove beneficial in the management of pancreatic cancer. |
format | Online Article Text |
id | pubmed-6178883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61788832018-10-12 Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways Pei, Chenlin He, Qun Liang, Shuai Gong, Xuejun Med Sci Monit Lab/In Vitro Research BACKGROUND: Pancreatic cancer causes tremendous mortality across the globe mainly due to late diagnosis and unavailability of efficient chemotheruptic agents. In the current study the anticancer potential of a plant derived alkaloid, Mahanimbine, was examined against a panel of pancreatic cancer cells. MATERIAL/METHODS: The cell proliferation was determined by MTT assay. Annexin V/PI and DAPI staining were performed to detect apoptosis. Cell cycle distribution was investigated by flow cytometery. Cell migration was detected by wound healing assay and protein expression was checked by western blotting. RESULTS: The results revealed that Mahanimbine could inhibit the proliferation of the all the pancreatic cancer cells with lower cytoxicity against the normal cells. The IC(50) ranged from 3.5 to 64 μM against the pancreatic cancer cell lines. The lowest IC(50) of 3.5 μM was observed tor the Capan-2 and SW119 pancreatic cancer cell lines. The anticancer activity of Mahanimbine against the Capan-2 and SW119 cells was found to be due to G(0)/G(1) cell cycle arrest and induction of apoptosis. Mahanimbine prompted apoptosis was also associated with decline in Bcl-2 and enhancement of the Bax expression. Further, it was observed that Mahanimbine could inhibit the AKT/mTOR and STAT3 signalling pathways in the Capan-2 and SW119 pancreatic cancer cells. The effects of the Mahanimbine were also examined on the migration of the Capan-2 and SW119 pancreatic cancer cells. It was found that Mahanimbine could inhibit the motility and migration of both the pancreatic cancer cell lines. CONCLUSIONS: We found that Mahanimbine inhibits the proliferation of pancreatic cancer cells and as such Mahanimbine may prove beneficial in the management of pancreatic cancer. International Scientific Literature, Inc. 2018-10-01 /pmc/articles/PMC6178883/ /pubmed/30273298 http://dx.doi.org/10.12659/MSM.911013 Text en © Med Sci Monit, 2018 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) ) |
spellingShingle | Lab/In Vitro Research Pei, Chenlin He, Qun Liang, Shuai Gong, Xuejun Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways |
title | Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways |
title_full | Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways |
title_fullStr | Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways |
title_full_unstemmed | Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways |
title_short | Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways |
title_sort | mahanimbine exerts anticancer effects on human pancreatic cancer cells by triggering cell cycle arrest, apoptosis, and modulation of akt/mammalian target of rapamycin (mtor) and signal transducer and activator of transcription 3 (stat3) signalling pathways |
topic | Lab/In Vitro Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178883/ https://www.ncbi.nlm.nih.gov/pubmed/30273298 http://dx.doi.org/10.12659/MSM.911013 |
work_keys_str_mv | AT peichenlin mahanimbineexertsanticancereffectsonhumanpancreaticcancercellsbytriggeringcellcyclearrestapoptosisandmodulationofaktmammaliantargetofrapamycinmtorandsignaltransducerandactivatoroftranscription3stat3signallingpathways AT hequn mahanimbineexertsanticancereffectsonhumanpancreaticcancercellsbytriggeringcellcyclearrestapoptosisandmodulationofaktmammaliantargetofrapamycinmtorandsignaltransducerandactivatoroftranscription3stat3signallingpathways AT liangshuai mahanimbineexertsanticancereffectsonhumanpancreaticcancercellsbytriggeringcellcyclearrestapoptosisandmodulationofaktmammaliantargetofrapamycinmtorandsignaltransducerandactivatoroftranscription3stat3signallingpathways AT gongxuejun mahanimbineexertsanticancereffectsonhumanpancreaticcancercellsbytriggeringcellcyclearrestapoptosisandmodulationofaktmammaliantargetofrapamycinmtorandsignaltransducerandactivatoroftranscription3stat3signallingpathways |