The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways

<p dir="ltr">In <u>colorectal cancer</u> (CRC), aberrations in <i>KRAS</i> are associated with aggressive tumorigenesis and an overall low <u>survival rate</u> because of chemoresistance and <u>adverse effects</u>. Ergo, complementary,...

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Main Author: Arij Fouzat Hassan (21767516) (author)
Other Authors: Ola Hussein (11449275) (author), Tara Al-Barazenji (18002491) (author), Asma Allouch (15430010) (author), Layla Kamareddine (121079) (author), Ahmed Malki (805714) (author), Ala‐Eddin Al Moustafa (21767519) (author), Ashraf Khalil (4591618) (author)
Published: 2024
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_version_ 1864513544589934592
author Arij Fouzat Hassan (21767516)
author2 Ola Hussein (11449275)
Tara Al-Barazenji (18002491)
Asma Allouch (15430010)
Layla Kamareddine (121079)
Ahmed Malki (805714)
Ala‐Eddin Al Moustafa (21767519)
Ashraf Khalil (4591618)
author2_role author
author
author
author
author
author
author
author_facet Arij Fouzat Hassan (21767516)
Ola Hussein (11449275)
Tara Al-Barazenji (18002491)
Asma Allouch (15430010)
Layla Kamareddine (121079)
Ahmed Malki (805714)
Ala‐Eddin Al Moustafa (21767519)
Ashraf Khalil (4591618)
author_role author
dc.creator.none.fl_str_mv Arij Fouzat Hassan (21767516)
Ola Hussein (11449275)
Tara Al-Barazenji (18002491)
Asma Allouch (15430010)
Layla Kamareddine (121079)
Ahmed Malki (805714)
Ala‐Eddin Al Moustafa (21767519)
Ashraf Khalil (4591618)
dc.date.none.fl_str_mv 2024-03-06T03:00:00Z
dc.identifier.none.fl_str_mv 10.1016/j.heliyon.2024.e27002
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/The_effect_of_novel_nitrogen-based_chalcone_analogs_on_colorectal_cancer_cells_Insight_into_the_molecular_pathways/29624909
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Colorectal cancer (CRC)
Chalcone
Nitrogen mustard
Methoxy
Analogs
Epithelial-mesenchymal transition (EMT)
dc.title.none.fl_str_mv The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">In <u>colorectal cancer</u> (CRC), aberrations in <i>KRAS</i> are associated with aggressive tumorigenesis and an overall low <u>survival rate</u> because of chemoresistance and <u>adverse effects</u>. Ergo, complementary, and integrative medicines are being considered for CRC treatment. Among which is the use of natural <u>chalcones</u> that are known to exhibit anti-tumor activities in KRAS mutant CRC subtypes treatment regimens. Consequently, we examine the effect of two novel compounds (DK13 and DK14) having chalcones with <u>nitrogen mustard</u> moiety on CRC cell lines (HCT-116 and LoVo) with <i>KRAS</i> mutation. These compounds were synthesized in our lab and previously reported to exhibit potent activity against breast cancer cells. Our data revealed that DK13 and DK14 treatment suppress cell growth, disturb the progression of cell cycle, and trigger apoptosis in CRC cell lines. Besides, treatment with both compounds impedes cell invasion and colony formation in both cell lines as compared to 5-FU; this is accompanied by up and down regulations of E-cadherin and <u>Vimentin</u>, respectively. At the molecular level, both compounds deregulate the expression and phosphorylation of β-catenin, Akt and mTOR, which are the main likely molecular mechanisms underlying these biological occurrences. Our findings present DK13 and DK14 as novel chemotherapies against CRC, through β-catenin/Akt/mTOR signaling pathways.</p><h2>Other Information</h2><p dir="ltr">Published in: Heliyon<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.heliyon.2024.e27002" target="_blank">https://dx.doi.org/10.1016/j.heliyon.2024.e27002</a></p>
eu_rights_str_mv openAccess
id Manara2_41b92fe82da2d16f0e3db5dc8e750a7f
identifier_str_mv 10.1016/j.heliyon.2024.e27002
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/29624909
publishDate 2024
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spelling The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathwaysArij Fouzat Hassan (21767516)Ola Hussein (11449275)Tara Al-Barazenji (18002491)Asma Allouch (15430010)Layla Kamareddine (121079)Ahmed Malki (805714)Ala‐Eddin Al Moustafa (21767519)Ashraf Khalil (4591618)Biomedical and clinical sciencesOncology and carcinogenesisPharmacology and pharmaceutical sciencesColorectal cancer (CRC)ChalconeNitrogen mustardMethoxyAnalogsEpithelial-mesenchymal transition (EMT)<p dir="ltr">In <u>colorectal cancer</u> (CRC), aberrations in <i>KRAS</i> are associated with aggressive tumorigenesis and an overall low <u>survival rate</u> because of chemoresistance and <u>adverse effects</u>. Ergo, complementary, and integrative medicines are being considered for CRC treatment. Among which is the use of natural <u>chalcones</u> that are known to exhibit anti-tumor activities in KRAS mutant CRC subtypes treatment regimens. Consequently, we examine the effect of two novel compounds (DK13 and DK14) having chalcones with <u>nitrogen mustard</u> moiety on CRC cell lines (HCT-116 and LoVo) with <i>KRAS</i> mutation. These compounds were synthesized in our lab and previously reported to exhibit potent activity against breast cancer cells. Our data revealed that DK13 and DK14 treatment suppress cell growth, disturb the progression of cell cycle, and trigger apoptosis in CRC cell lines. Besides, treatment with both compounds impedes cell invasion and colony formation in both cell lines as compared to 5-FU; this is accompanied by up and down regulations of E-cadherin and <u>Vimentin</u>, respectively. At the molecular level, both compounds deregulate the expression and phosphorylation of β-catenin, Akt and mTOR, which are the main likely molecular mechanisms underlying these biological occurrences. Our findings present DK13 and DK14 as novel chemotherapies against CRC, through β-catenin/Akt/mTOR signaling pathways.</p><h2>Other Information</h2><p dir="ltr">Published in: Heliyon<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.heliyon.2024.e27002" target="_blank">https://dx.doi.org/10.1016/j.heliyon.2024.e27002</a></p>2024-03-06T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.heliyon.2024.e27002https://figshare.com/articles/journal_contribution/The_effect_of_novel_nitrogen-based_chalcone_analogs_on_colorectal_cancer_cells_Insight_into_the_molecular_pathways/29624909CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/296249092024-03-06T03:00:00Z
spellingShingle The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways
Arij Fouzat Hassan (21767516)
Biomedical and clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Colorectal cancer (CRC)
Chalcone
Nitrogen mustard
Methoxy
Analogs
Epithelial-mesenchymal transition (EMT)
status_str publishedVersion
title The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways
title_full The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways
title_fullStr The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways
title_full_unstemmed The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways
title_short The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways
title_sort The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways
topic Biomedical and clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Colorectal cancer (CRC)
Chalcone
Nitrogen mustard
Methoxy
Analogs
Epithelial-mesenchymal transition (EMT)