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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2024
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| 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 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| 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) |