Ponatinib and gossypol act in synergy to suppress colorectal cancer cells by modulating apoptosis/autophagy crosstalk and inhibiting the FGF19/FGFR4 axis
Objective: To evaluate the efficacy of ponatinib plus gossypol against colorectal cancer HCT-116 and Caco-2 cells. Methods: Cells were treated with ponatinib and/or gossypol at increasing concentrations to evaluate synergistic drug interactions by combination index. Cell viability, FGF19/FGFR4, and...
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Wolters Kluwer Medknow Publications
2023
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ftdoajarticles:oai:doaj.org/article:2f1fb73d2d7b4194aed97491201d210b 2024-09-09T19:26:48+00:00 Ponatinib and gossypol act in synergy to suppress colorectal cancer cells by modulating apoptosis/autophagy crosstalk and inhibiting the FGF19/FGFR4 axis Naglaa M El-Lakkany Hadeel H Elkattan Alaa E Elsisi 2023-01-01T00:00:00Z https://doi.org/10.4103/2221-1691.372286 https://doaj.org/article/2f1fb73d2d7b4194aed97491201d210b EN eng Wolters Kluwer Medknow Publications http://www.apjtb.org/article.asp?issn=2221-1691;year=2023;volume=13;issue=3;spage=131;epage=138;aulast=El-Lakkany https://doaj.org/toc/2221-1691 https://doaj.org/toc/2588-9222 2221-1691 2588-9222 doi:10.4103/2221-1691.372286 https://doaj.org/article/2f1fb73d2d7b4194aed97491201d210b Asian Pacific Journal of Tropical Biomedicine, Vol 13, Iss 3, Pp 131-138 (2023) autophagy apoptosis cell viability fgf19/fgfr4 gossypol ponatinib hct-116 caco-2 colorectal cancer Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 article 2023 ftdoajarticles https://doi.org/10.4103/2221-1691.372286 2024-08-05T17:49:19Z Objective: To evaluate the efficacy of ponatinib plus gossypol against colorectal cancer HCT-116 and Caco-2 cells. Methods: Cells were treated with ponatinib and/or gossypol at increasing concentrations to evaluate synergistic drug interactions by combination index. Cell viability, FGF19/FGFR4, and apoptotic and autophagic cell death were studied. Results: Ponatinib (1.25-40 μM) and gossypol (2.5-80 μM) monotherapy inhibited HCT-116 and Caco-2 cell viability in a dose- and time-dependent manner. The combination of ponatinib and gossypol at a ratio of 1 to 2 significantly decreased cell viability (P<0.05), with a > 2- and > 4-fold reduction in IC50, respectively, after 24 h and 48 h, as compared to the IC50 of ponatinib. Lower combined concentrations showed greater synergism (combination index<1) with a higher ponatinib dose reduction index. Moreover, ponatinib plus gossypol induced morphological changes in HCT-116 and Caco-2 cells, increased beclin-1 and caspase-3, and decreased FGF19, FGFR4, Bcl-2 and p-Akt as compared to treatment with drugs alone. Conclusions: Gossypol enhances ponatinib's anticancer effects against colorectal cancer cells through antiproliferative, apoptotic, and autophagic mechanisms. This may open the way for the future use of ponatinib at lower doses with gossypol as a potentially safer targeted strategy for colorectal cancer treatment. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Asian Pacific Journal of Tropical Biomedicine 13 3 131 138 |
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autophagy apoptosis cell viability fgf19/fgfr4 gossypol ponatinib hct-116 caco-2 colorectal cancer Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 |
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autophagy apoptosis cell viability fgf19/fgfr4 gossypol ponatinib hct-116 caco-2 colorectal cancer Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 Naglaa M El-Lakkany Hadeel H Elkattan Alaa E Elsisi Ponatinib and gossypol act in synergy to suppress colorectal cancer cells by modulating apoptosis/autophagy crosstalk and inhibiting the FGF19/FGFR4 axis |
topic_facet |
autophagy apoptosis cell viability fgf19/fgfr4 gossypol ponatinib hct-116 caco-2 colorectal cancer Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 |
description |
Objective: To evaluate the efficacy of ponatinib plus gossypol against colorectal cancer HCT-116 and Caco-2 cells. Methods: Cells were treated with ponatinib and/or gossypol at increasing concentrations to evaluate synergistic drug interactions by combination index. Cell viability, FGF19/FGFR4, and apoptotic and autophagic cell death were studied. Results: Ponatinib (1.25-40 μM) and gossypol (2.5-80 μM) monotherapy inhibited HCT-116 and Caco-2 cell viability in a dose- and time-dependent manner. The combination of ponatinib and gossypol at a ratio of 1 to 2 significantly decreased cell viability (P<0.05), with a > 2- and > 4-fold reduction in IC50, respectively, after 24 h and 48 h, as compared to the IC50 of ponatinib. Lower combined concentrations showed greater synergism (combination index<1) with a higher ponatinib dose reduction index. Moreover, ponatinib plus gossypol induced morphological changes in HCT-116 and Caco-2 cells, increased beclin-1 and caspase-3, and decreased FGF19, FGFR4, Bcl-2 and p-Akt as compared to treatment with drugs alone. Conclusions: Gossypol enhances ponatinib's anticancer effects against colorectal cancer cells through antiproliferative, apoptotic, and autophagic mechanisms. This may open the way for the future use of ponatinib at lower doses with gossypol as a potentially safer targeted strategy for colorectal cancer treatment. |
format |
Article in Journal/Newspaper |
author |
Naglaa M El-Lakkany Hadeel H Elkattan Alaa E Elsisi |
author_facet |
Naglaa M El-Lakkany Hadeel H Elkattan Alaa E Elsisi |
author_sort |
Naglaa M El-Lakkany |
title |
Ponatinib and gossypol act in synergy to suppress colorectal cancer cells by modulating apoptosis/autophagy crosstalk and inhibiting the FGF19/FGFR4 axis |
title_short |
Ponatinib and gossypol act in synergy to suppress colorectal cancer cells by modulating apoptosis/autophagy crosstalk and inhibiting the FGF19/FGFR4 axis |
title_full |
Ponatinib and gossypol act in synergy to suppress colorectal cancer cells by modulating apoptosis/autophagy crosstalk and inhibiting the FGF19/FGFR4 axis |
title_fullStr |
Ponatinib and gossypol act in synergy to suppress colorectal cancer cells by modulating apoptosis/autophagy crosstalk and inhibiting the FGF19/FGFR4 axis |
title_full_unstemmed |
Ponatinib and gossypol act in synergy to suppress colorectal cancer cells by modulating apoptosis/autophagy crosstalk and inhibiting the FGF19/FGFR4 axis |
title_sort |
ponatinib and gossypol act in synergy to suppress colorectal cancer cells by modulating apoptosis/autophagy crosstalk and inhibiting the fgf19/fgfr4 axis |
publisher |
Wolters Kluwer Medknow Publications |
publishDate |
2023 |
url |
https://doi.org/10.4103/2221-1691.372286 https://doaj.org/article/2f1fb73d2d7b4194aed97491201d210b |
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Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Asian Pacific Journal of Tropical Biomedicine, Vol 13, Iss 3, Pp 131-138 (2023) |
op_relation |
http://www.apjtb.org/article.asp?issn=2221-1691;year=2023;volume=13;issue=3;spage=131;epage=138;aulast=El-Lakkany https://doaj.org/toc/2221-1691 https://doaj.org/toc/2588-9222 2221-1691 2588-9222 doi:10.4103/2221-1691.372286 https://doaj.org/article/2f1fb73d2d7b4194aed97491201d210b |
op_doi |
https://doi.org/10.4103/2221-1691.372286 |
container_title |
Asian Pacific Journal of Tropical Biomedicine |
container_volume |
13 |
container_issue |
3 |
container_start_page |
131 |
op_container_end_page |
138 |
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1809896349774118912 |