Novel Nitrogen-Based Chalcone Analogs Provoke Substantial Apoptosis in HER2-Positive Human Breast Cancer Cells via JNK and ERK1/ERK2 Signaling Pathways
Natural chalcones possess antitumor properties and play a role as inducers of apoptosis, antioxidants and cytotoxic compounds. We recently reported that novel nitrogen chalcone-based compounds, which were generated in our lab, have specific effects on triple-negative breast cancer cells. However, th...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9621 |
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| author | Balsam Rizeq Ishita Gupta Hadeel Kheraldine Dana Elkhalifa Halema F. Al-Farsi Ala-Eddin Al Moustafa Ashraf Khalil |
| author_facet | Balsam Rizeq Ishita Gupta Hadeel Kheraldine Dana Elkhalifa Halema F. Al-Farsi Ala-Eddin Al Moustafa Ashraf Khalil |
| author_sort | Balsam Rizeq |
| collection | DOAJ |
| description | Natural chalcones possess antitumor properties and play a role as inducers of apoptosis, antioxidants and cytotoxic compounds. We recently reported that novel nitrogen chalcone-based compounds, which were generated in our lab, have specific effects on triple-negative breast cancer cells. However, the outcome of these two new compounds on human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains nascent. Thus, we herein investigated the effects of these compounds (DK-13 and DK-14) on two HER2-positive breast cancer cell lines, SKBR3 and ZR75. Our data revealed that these compounds inhibit cell proliferation, deregulate cell-cycle progression and significantly induce cell apoptosis in both cell lines. Furthermore, the two chalcone compounds cause a significant reduction in the cell invasion ability of SKBR3 and ZR75 cancer cells. In parallel, we found that DK-13 and DK-14 inhibit colony formation of both cell lines in comparison to their matched controls. On the other hand, we noticed that these two compounds can inhibit angiogenesis in the chorioallantoic membrane model. The molecular pathway analysis of chalcone compounds exposed cells revealed that these compounds inhibit the expression of both JNK1/2/3 and ERK1/2, the major plausible molecular pathways behind these events. Our findings implicate that DK-13 and DK-14 possess effective chemotherapeutic outcomes against HER2-positive breast cancer via the ERK1/2 and JNK1/2/3 signaling pathways. |
| first_indexed | 2024-03-10T08:09:34Z |
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| id | doaj.art-34c8ca6b503743929cafbd9d7509d09c |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:09:34Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-34c8ca6b503743929cafbd9d7509d09c2023-11-22T10:46:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012217962110.3390/ijms22179621Novel Nitrogen-Based Chalcone Analogs Provoke Substantial Apoptosis in HER2-Positive Human Breast Cancer Cells via JNK and ERK1/ERK2 Signaling PathwaysBalsam Rizeq0Ishita Gupta1Hadeel Kheraldine2Dana Elkhalifa3Halema F. Al-Farsi4Ala-Eddin Al Moustafa5Ashraf Khalil6College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, QatarCollege of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, QatarCollege of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, QatarDepartment of Pharmacy, Aspetar Orthopedic and Sports Medicine Hospital, Doha P.O. Box 2713, QatarCollege of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, QatarCollege of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, QatarBiomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha P.O. Box 2713, QatarNatural chalcones possess antitumor properties and play a role as inducers of apoptosis, antioxidants and cytotoxic compounds. We recently reported that novel nitrogen chalcone-based compounds, which were generated in our lab, have specific effects on triple-negative breast cancer cells. However, the outcome of these two new compounds on human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains nascent. Thus, we herein investigated the effects of these compounds (DK-13 and DK-14) on two HER2-positive breast cancer cell lines, SKBR3 and ZR75. Our data revealed that these compounds inhibit cell proliferation, deregulate cell-cycle progression and significantly induce cell apoptosis in both cell lines. Furthermore, the two chalcone compounds cause a significant reduction in the cell invasion ability of SKBR3 and ZR75 cancer cells. In parallel, we found that DK-13 and DK-14 inhibit colony formation of both cell lines in comparison to their matched controls. On the other hand, we noticed that these two compounds can inhibit angiogenesis in the chorioallantoic membrane model. The molecular pathway analysis of chalcone compounds exposed cells revealed that these compounds inhibit the expression of both JNK1/2/3 and ERK1/2, the major plausible molecular pathways behind these events. Our findings implicate that DK-13 and DK-14 possess effective chemotherapeutic outcomes against HER2-positive breast cancer via the ERK1/2 and JNK1/2/3 signaling pathways.https://www.mdpi.com/1422-0067/22/17/9621chalconesHER2-positivebreast cancerchemopreventionapoptosis |
| spellingShingle | Balsam Rizeq Ishita Gupta Hadeel Kheraldine Dana Elkhalifa Halema F. Al-Farsi Ala-Eddin Al Moustafa Ashraf Khalil Novel Nitrogen-Based Chalcone Analogs Provoke Substantial Apoptosis in HER2-Positive Human Breast Cancer Cells via JNK and ERK1/ERK2 Signaling Pathways International Journal of Molecular Sciences chalcones HER2-positive breast cancer chemoprevention apoptosis |
| title | Novel Nitrogen-Based Chalcone Analogs Provoke Substantial Apoptosis in HER2-Positive Human Breast Cancer Cells via JNK and ERK1/ERK2 Signaling Pathways |
| title_full | Novel Nitrogen-Based Chalcone Analogs Provoke Substantial Apoptosis in HER2-Positive Human Breast Cancer Cells via JNK and ERK1/ERK2 Signaling Pathways |
| title_fullStr | Novel Nitrogen-Based Chalcone Analogs Provoke Substantial Apoptosis in HER2-Positive Human Breast Cancer Cells via JNK and ERK1/ERK2 Signaling Pathways |
| title_full_unstemmed | Novel Nitrogen-Based Chalcone Analogs Provoke Substantial Apoptosis in HER2-Positive Human Breast Cancer Cells via JNK and ERK1/ERK2 Signaling Pathways |
| title_short | Novel Nitrogen-Based Chalcone Analogs Provoke Substantial Apoptosis in HER2-Positive Human Breast Cancer Cells via JNK and ERK1/ERK2 Signaling Pathways |
| title_sort | novel nitrogen based chalcone analogs provoke substantial apoptosis in her2 positive human breast cancer cells via jnk and erk1 erk2 signaling pathways |
| topic | chalcones HER2-positive breast cancer chemoprevention apoptosis |
| url | https://www.mdpi.com/1422-0067/22/17/9621 |
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