Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines
In cancer management, drug resistance remains a challenge that reduces the effectiveness of chemotherapy. Several studies have shown that curcumin resensitizes cancer cells to chemotherapeutic drugs to overcome resistance. In the present study, we investigate the potential therapeutic role of curcum...
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MDPI AG
2022-09-01
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| author | Sami A. Gabr Wael M. Elsaed Mohamed Ahmed Eladl Mohamed El-Sherbiny Hasnaa Ali Ebrahim Saad Mohamed Asseri Yasir A. M. Eltahir Nehal Elsherbiny Mamdouh Eldesoqui |
| author_facet | Sami A. Gabr Wael M. Elsaed Mohamed Ahmed Eladl Mohamed El-Sherbiny Hasnaa Ali Ebrahim Saad Mohamed Asseri Yasir A. M. Eltahir Nehal Elsherbiny Mamdouh Eldesoqui |
| author_sort | Sami A. Gabr |
| collection | DOAJ |
| description | In cancer management, drug resistance remains a challenge that reduces the effectiveness of chemotherapy. Several studies have shown that curcumin resensitizes cancer cells to chemotherapeutic drugs to overcome resistance. In the present study, we investigate the potential therapeutic role of curcumin in regulating the proliferation of drug-resistant cancers. Six drug-sensitive (MCF7, HCT116, and A549) and -resistant (MCF7/TH, HCT116R, and A549/ADR) cancer cell lines were treated with curcumin followed by an analysis of cytotoxicity, LDH enzyme, total reactive oxygen species, antioxidant enzymes (SOD and CAT), fibrosis markers (TGF-β1 protein, fibronectin, and hydroxyproline), and expression of cellular apoptotic markers (Bcl-2, Bax, Bax/Bcl-2 ratio, Annexin V, cytochrome c, and caspase-8). Additionally, the expression of cellular SIRT1 was estimated by ELISA and RT-PCR analysis. Curcumin treatment at doses of 2.7–54.3 µM significantly reduced the growth of sensitive and resistant cells as supported with decreased viability and increased cellular LDH enzyme of treated cells compared to controls non-treated cells. Curcumin also at doses of 2.7 and 54.3 µM regulated the fibrogenesis by reducing the expression of fibrotic markers in treated cells. Analysis of apoptotic markers indicated increased Bax, Bax, Bax/Bcl-2 ratio, Annexin V, caspase-8, and cytochrome c expression, while Bcl-2 expressions were significantly reduced. In curcumin-treated cells at 2.7 μM, non-significant change in ROS with significant increase in SOD and CAT activity was observed, whereas an increase in ROS with a reduction in respective antioxidant enzymes were seen at higher concentrations along with significant upregulation of SIRT1. In conclusion, the present study shows that curcumin induces anticancer activity against resistant cancer cell lines in a concentration- and time-dependent manner. The protective activities of curcumin against the growth of cancer cells are mediated by modulating oxidative stress, regulating fibrosis, SIRT1 activation, and inducing cellular apoptosis. Therefore, curcumin could be tested as an auxiliary therapeutic agent to improve the prognosis in patients with resistant cancers. |
| first_indexed | 2024-03-09T23:22:38Z |
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| language | English |
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| spelling | doaj.art-987df854cd05424e902a42d82c603c6e2023-11-23T17:23:56ZengMDPI AGLife2075-17292022-09-01129142710.3390/life12091427Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell LinesSami A. Gabr0Wael M. Elsaed1Mohamed Ahmed Eladl2Mohamed El-Sherbiny3Hasnaa Ali Ebrahim4Saad Mohamed Asseri5Yasir A. M. Eltahir6Nehal Elsherbiny7Mamdouh Eldesoqui8Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesDepartment of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi ArabiaDepartment of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Clinical Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi ArabiaDepartment of Respiratory Care, College of Applied Sciences, AlMaarefa University, Riyadh 11597, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, P.O. Box 741, Tabuk 71491, Saudi ArabiaDepartment of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptIn cancer management, drug resistance remains a challenge that reduces the effectiveness of chemotherapy. Several studies have shown that curcumin resensitizes cancer cells to chemotherapeutic drugs to overcome resistance. In the present study, we investigate the potential therapeutic role of curcumin in regulating the proliferation of drug-resistant cancers. Six drug-sensitive (MCF7, HCT116, and A549) and -resistant (MCF7/TH, HCT116R, and A549/ADR) cancer cell lines were treated with curcumin followed by an analysis of cytotoxicity, LDH enzyme, total reactive oxygen species, antioxidant enzymes (SOD and CAT), fibrosis markers (TGF-β1 protein, fibronectin, and hydroxyproline), and expression of cellular apoptotic markers (Bcl-2, Bax, Bax/Bcl-2 ratio, Annexin V, cytochrome c, and caspase-8). Additionally, the expression of cellular SIRT1 was estimated by ELISA and RT-PCR analysis. Curcumin treatment at doses of 2.7–54.3 µM significantly reduced the growth of sensitive and resistant cells as supported with decreased viability and increased cellular LDH enzyme of treated cells compared to controls non-treated cells. Curcumin also at doses of 2.7 and 54.3 µM regulated the fibrogenesis by reducing the expression of fibrotic markers in treated cells. Analysis of apoptotic markers indicated increased Bax, Bax, Bax/Bcl-2 ratio, Annexin V, caspase-8, and cytochrome c expression, while Bcl-2 expressions were significantly reduced. In curcumin-treated cells at 2.7 μM, non-significant change in ROS with significant increase in SOD and CAT activity was observed, whereas an increase in ROS with a reduction in respective antioxidant enzymes were seen at higher concentrations along with significant upregulation of SIRT1. In conclusion, the present study shows that curcumin induces anticancer activity against resistant cancer cell lines in a concentration- and time-dependent manner. The protective activities of curcumin against the growth of cancer cells are mediated by modulating oxidative stress, regulating fibrosis, SIRT1 activation, and inducing cellular apoptosis. Therefore, curcumin could be tested as an auxiliary therapeutic agent to improve the prognosis in patients with resistant cancers.https://www.mdpi.com/2075-1729/12/9/1427cancer resistanceoxidative stressapoptosiscurcumin activitySIRT1 activation |
| spellingShingle | Sami A. Gabr Wael M. Elsaed Mohamed Ahmed Eladl Mohamed El-Sherbiny Hasnaa Ali Ebrahim Saad Mohamed Asseri Yasir A. M. Eltahir Nehal Elsherbiny Mamdouh Eldesoqui Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines Life cancer resistance oxidative stress apoptosis curcumin activity SIRT1 activation |
| title | Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines |
| title_full | Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines |
| title_fullStr | Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines |
| title_full_unstemmed | Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines |
| title_short | Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines |
| title_sort | curcumin modulates oxidative stress fibrosis and apoptosis in drug resistant cancer cell lines |
| topic | cancer resistance oxidative stress apoptosis curcumin activity SIRT1 activation |
| url | https://www.mdpi.com/2075-1729/12/9/1427 |
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