Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line
Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, it provides a...
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MDPI AG
2023-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/2/557 |
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| author | Afshan Shams Ayaz Ahmed Ajmal Khan Shariqa Khawaja Najeeb Ur Rehman Asma Saleem Qazi Adnan Khan Sami Bawazeer Syed Abid Ali Ahmed Al-Harrasi |
| author_facet | Afshan Shams Ayaz Ahmed Ajmal Khan Shariqa Khawaja Najeeb Ur Rehman Asma Saleem Qazi Adnan Khan Sami Bawazeer Syed Abid Ali Ahmed Al-Harrasi |
| author_sort | Afshan Shams |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, it provides a window to look for more biocompatible alternatives. In this study, two natural compounds, costunolide (CE) and aloe emodin (AE), were isolated from the stem of <i>Lycium shawii.</i> The compounds were examined for their anticancer and apoptotic potentials against OSCC (CAL 27) cells, using an in vitro analysis, such as a MTT assay, scratch assay, gene, and protein expressions. Both compounds, CE and AE, were found to be cytotoxic against the cancer cells with an IC<sub>50</sub> value of 32 and 38 µM, respectively. Moreover, the compounds were found to be non-toxic against normal NIH-3T3 cells and comparable with the standard drug i.e., 5-fluorouracil (IC<sub>50</sub> = 97.76 µM). These compounds were active against normal cells at higher concentrations. Nuclear staining displayed the presence of apoptosis-associated morphological changes, i.e., karyopyknosis and karyorrhexis in the treated cancer cells. Flow cytometry results further confirmed that these compounds induce apoptosis rather than necrosis, as the majority of the cells were found in the late apoptotic phase. Gene and protein expression analyses showed an increased expression of apoptotic genes, i.e., BAK, caspase 3, 6, and 9. Moreover, the compounds significantly downregulated the expression of the anti-apoptotic (BCL-2 L1), metastatic (MMP-2), and pro-inflammatory (COX-2) genes. Both compounds have shown promising anticancer, apoptotic, and anti-migratory activities against the OSCC cell line (i.e., CAL-27). However, further in vivo studies are required to explore these compounds as anticancer agents. |
| first_indexed | 2024-03-09T13:16:15Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:16:15Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
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| series | Cancers |
| spelling | doaj.art-3829c626588f4fc5b72e68a11c9cc3882023-11-30T21:35:35ZengMDPI AGCancers2072-66942023-01-0115255710.3390/cancers15020557Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell LineAfshan Shams0Ayaz Ahmed1Ajmal Khan2Shariqa Khawaja3Najeeb Ur Rehman4Asma Saleem Qazi5Adnan Khan6Sami Bawazeer7Syed Abid Ali8Ahmed Al-Harrasi9Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanDr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanNatural and Medical Sciences Research Center, University of Nizwa, Birkat-Al-Mouz, P.O. Box 33, Nizwa 616, OmanDr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanNatural and Medical Sciences Research Center, University of Nizwa, Birkat-Al-Mouz, P.O. Box 33, Nizwa 616, OmanDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, PakistanDepartment of Microbiology, University of Karachi, Karachi 75270, PakistanDepartment of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi ArabiaThird World Center for Science and Technology, H.E.J. Research Institute of Chemistry, University of Karachi, Karachi 75270, PakistanNatural and Medical Sciences Research Center, University of Nizwa, Birkat-Al-Mouz, P.O. Box 33, Nizwa 616, OmanOral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, it provides a window to look for more biocompatible alternatives. In this study, two natural compounds, costunolide (CE) and aloe emodin (AE), were isolated from the stem of <i>Lycium shawii.</i> The compounds were examined for their anticancer and apoptotic potentials against OSCC (CAL 27) cells, using an in vitro analysis, such as a MTT assay, scratch assay, gene, and protein expressions. Both compounds, CE and AE, were found to be cytotoxic against the cancer cells with an IC<sub>50</sub> value of 32 and 38 µM, respectively. Moreover, the compounds were found to be non-toxic against normal NIH-3T3 cells and comparable with the standard drug i.e., 5-fluorouracil (IC<sub>50</sub> = 97.76 µM). These compounds were active against normal cells at higher concentrations. Nuclear staining displayed the presence of apoptosis-associated morphological changes, i.e., karyopyknosis and karyorrhexis in the treated cancer cells. Flow cytometry results further confirmed that these compounds induce apoptosis rather than necrosis, as the majority of the cells were found in the late apoptotic phase. Gene and protein expression analyses showed an increased expression of apoptotic genes, i.e., BAK, caspase 3, 6, and 9. Moreover, the compounds significantly downregulated the expression of the anti-apoptotic (BCL-2 L1), metastatic (MMP-2), and pro-inflammatory (COX-2) genes. Both compounds have shown promising anticancer, apoptotic, and anti-migratory activities against the OSCC cell line (i.e., CAL-27). However, further in vivo studies are required to explore these compounds as anticancer agents.https://www.mdpi.com/2072-6694/15/2/557oral squamous cell carcinomacostunolidealoe emodin<i>Lycium shawii</i>caspaseanti-apoptotic |
| spellingShingle | Afshan Shams Ayaz Ahmed Ajmal Khan Shariqa Khawaja Najeeb Ur Rehman Asma Saleem Qazi Adnan Khan Sami Bawazeer Syed Abid Ali Ahmed Al-Harrasi Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line Cancers oral squamous cell carcinoma costunolide aloe emodin <i>Lycium shawii</i> caspase anti-apoptotic |
| title | Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line |
| title_full | Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line |
| title_fullStr | Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line |
| title_full_unstemmed | Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line |
| title_short | Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line |
| title_sort | naturally isolated sesquiterpene lactone and hydroxyanthraquinone induce apoptosis in oral squamous cell carcinoma cell line |
| topic | oral squamous cell carcinoma costunolide aloe emodin <i>Lycium shawii</i> caspase anti-apoptotic |
| url | https://www.mdpi.com/2072-6694/15/2/557 |
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