Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling Molecules
Beta-Caryophyllene (BCP), a natural bicyclic sesquiterpenes, is an abundant biomolecule in red pepper and other plants. Recently, it was reported to reduce the growth and the proliferation as well as enhance the apoptosis in numerous cancer cells, including colorectal, ovarian, bladder cancer and lu...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/23/8354 |
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| author | Emad A. Ahmed Hamad Abu Zahra Rebai Ben Ammar Maged Elsayed Mohamed Hairul-Islam M. Ibrahim |
| author_facet | Emad A. Ahmed Hamad Abu Zahra Rebai Ben Ammar Maged Elsayed Mohamed Hairul-Islam M. Ibrahim |
| author_sort | Emad A. Ahmed |
| collection | DOAJ |
| description | Beta-Caryophyllene (BCP), a natural bicyclic sesquiterpenes, is an abundant biomolecule in red pepper and other plants. Recently, it was reported to reduce the growth and the proliferation as well as enhance the apoptosis in numerous cancer cells, including colorectal, ovarian, bladder cancer and lung cancer. On the other hand, the combination therapy of cisplatin (CDDP) with other phytochemical compounds has synergistically enhanced the killing effect of CDDP on several types of cancer. In the current model, we have tested the role of BCP in enhancing the anti-tumor activity of CDDP on lung cancer cell lines. The results showed that BCP is not toxic at moderate doses and it can prevent lung cancer progression in doses above 75 µM. However, when being combined with CDDP, BCP improved the former chemotherapeutic function through regulating cell cycle, apoptosis and EMT signaling molecules. Gene and protein expression analysis showed that the combined treatment of CDDP and BCP significantly upregulated the level of the cyclin-dependent kinase inhibitor, CDKN1A, and the inhibitor of the apoptosis, BCL-xl2. In addition, the combination treatment reduced the protein level of the apoptosis regulator, BCL-2. Moreover, BCP appears to prohibit the EMT process that is associated with CDDP chemotherapy since the combination treatment induced a significant increase in the level of the epithelial cell marker E-cad that was reduced in CDDP-treated cells. In agreement with that, the combined treatment managed to modulate the effect of CDDP on the mesenchymal transcription factor ZEB-2. Additionally, molecular docking has been conducted to check the virtual interaction of BCP with these and other signaling molecules, but only cyclin-dependent kinase CDK6 was found to virtually bind with BCP, and at four sites with higher and stable biding energy (−7.8). Together, these data indicate that BCP enhances CDDP chemotherapeutic function through regulating the cell cycle, the apoptosis and EMT signaling molecules. |
| first_indexed | 2024-03-09T17:40:05Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-09T17:40:05Z |
| publishDate | 2022-11-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-d9ee0792bc1d424ea9e01cc232901bd82023-11-24T11:40:51ZengMDPI AGMolecules1420-30492022-11-012723835410.3390/molecules27238354Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling MoleculesEmad A. Ahmed0Hamad Abu Zahra1Rebai Ben Ammar2Maged Elsayed Mohamed3Hairul-Islam M. Ibrahim4Biological Sciences Department, College of Science, King Faisal University, Al-Ahsa 31982, Saudi ArabiaBiological Sciences Department, College of Science, King Faisal University, Al-Ahsa 31982, Saudi ArabiaBiological Sciences Department, College of Science, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaBiological Sciences Department, College of Science, King Faisal University, Al-Ahsa 31982, Saudi ArabiaBeta-Caryophyllene (BCP), a natural bicyclic sesquiterpenes, is an abundant biomolecule in red pepper and other plants. Recently, it was reported to reduce the growth and the proliferation as well as enhance the apoptosis in numerous cancer cells, including colorectal, ovarian, bladder cancer and lung cancer. On the other hand, the combination therapy of cisplatin (CDDP) with other phytochemical compounds has synergistically enhanced the killing effect of CDDP on several types of cancer. In the current model, we have tested the role of BCP in enhancing the anti-tumor activity of CDDP on lung cancer cell lines. The results showed that BCP is not toxic at moderate doses and it can prevent lung cancer progression in doses above 75 µM. However, when being combined with CDDP, BCP improved the former chemotherapeutic function through regulating cell cycle, apoptosis and EMT signaling molecules. Gene and protein expression analysis showed that the combined treatment of CDDP and BCP significantly upregulated the level of the cyclin-dependent kinase inhibitor, CDKN1A, and the inhibitor of the apoptosis, BCL-xl2. In addition, the combination treatment reduced the protein level of the apoptosis regulator, BCL-2. Moreover, BCP appears to prohibit the EMT process that is associated with CDDP chemotherapy since the combination treatment induced a significant increase in the level of the epithelial cell marker E-cad that was reduced in CDDP-treated cells. In agreement with that, the combined treatment managed to modulate the effect of CDDP on the mesenchymal transcription factor ZEB-2. Additionally, molecular docking has been conducted to check the virtual interaction of BCP with these and other signaling molecules, but only cyclin-dependent kinase CDK6 was found to virtually bind with BCP, and at four sites with higher and stable biding energy (−7.8). Together, these data indicate that BCP enhances CDDP chemotherapeutic function through regulating the cell cycle, the apoptosis and EMT signaling molecules.https://www.mdpi.com/1420-3049/27/23/8354Beta-Caryophyllene (BCP)cisplatinsynergistic chemotherapylung cancer cell linesA549 |
| spellingShingle | Emad A. Ahmed Hamad Abu Zahra Rebai Ben Ammar Maged Elsayed Mohamed Hairul-Islam M. Ibrahim Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling Molecules Molecules Beta-Caryophyllene (BCP) cisplatin synergistic chemotherapy lung cancer cell lines A549 |
| title | Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling Molecules |
| title_full | Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling Molecules |
| title_fullStr | Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling Molecules |
| title_full_unstemmed | Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling Molecules |
| title_short | Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling Molecules |
| title_sort | beta caryophyllene enhances the anti tumor activity of cisplatin in lung cancer cell lines through regulating cell cycle and apoptosis signaling molecules |
| topic | Beta-Caryophyllene (BCP) cisplatin synergistic chemotherapy lung cancer cell lines A549 |
| url | https://www.mdpi.com/1420-3049/27/23/8354 |
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