Thymoquinone-chemotherapeutic combinations: new regimen to combat cancer and cancer stem cells

El‐Far, Ali H.; Tantawy, Mohamed A.; Jaouni, Soad K. Al; Mousa, Shaker A.

doi:10.1007/s00210-020-01898-y

Cited by 33 publications

(26 citation statements)

References 128 publications

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“…Thymoquinone (TQ) is the active constituent of black seed (Nigella sativa) which is the homologue of ubiquinone and plays its role in the mitochondrial respiratory chain [14]. Anticancer, antioxidant, and antimicrobial activities are regarded as the main function of TQ [15]. When it comes to cancer therapy, this component plays its anticancer role in different ways including the prevention of oncogenic signaling pathways and the induction of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Thymoquinone Augments Methotrexate-Induced Apoptosis on Osteosarcoma Cells

et al. 2022

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Background Osteosarcoma (OS) as the most frequent primary bone malignancy in children and adolescents has a short survival rate in advanced stages. Alternative herbal medicines with fewer side effects or the potency to protect common therapy’s side effects can be helpful in combinational therapies. Herein, we aim to explore the effects of Thymoquinone (TQ) combined with Methotrexate (MTX) on Saos-2 cells apoptosis. Methods The effects of TQ and MTX alone or in combination on Saos-2 cell viability were measured by MTT assay. Real-time PCR was applied for the measurement of Bax, BCL-2, and caspase-9 mRNA expression. Apoptosis evaluation was conducted by flow cytometry. Results TQ improves the cytotoxic effects of MTX on Saos-2 cells proliferation at lower doses. Indeed, the IC50 of MTX decreased from 26 μM to 15 μM when it combined with TQ. TQ and MTX can induce the expression level of pro-apoptotic factors, Bax and caspase-9 while inhibiting anti-apoptotic protein BCL-2. Moreover, the combination of TQ and MTX potentiates apoptosis to 73%, compared to either TQ (48%) or MTX (53%) treated cells. Conclusion The co-treatment of TQ and MTX is associated with the up-regulation of apoptotic factors and down-regulation of anti-apoptotic factors, conducting apoptosis aggravation and OS cell death.

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Section: Discussionmentioning

confidence: 99%

Thymoquinone Augments Methotrexate-Induced Apoptosis on Osteosarcoma Cells

et al. 2022

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“…For instance, TQ suppresses PI3K/Akt signal transduction in MDA-MB-468 and T-47D breast [ 5 ], induces p53/p21 expression in HCT-116 colon, and induces caspase-dependent apoptosis in A549 lung carcinoma cells [ 6 ]; it also inhibits bone metastasis of breast MDA-MB-231 cells [ 7 ]. Moreover, TQ can be used as an adjuvant agent that sensitises cancer cells to chemotherapy by suppressing resistance mechanisms [ 8 , 9 ]. Effenberger et al (2010) found that TQ improved doxorubicin potency against leukaemic HL-60 cells and enhanced sensitivity of multi-drug resistant MCF cells to topotecan [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Concurrent Reactive Oxygen Species Generation and Aneuploidy Induction Contribute to Thymoquinone Anticancer Activity

et al. 2021

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Thymoquinone (TQ) is the main biologically active constituent of Nigella sativa. Many studies have confirmed its anticancer actions. Herein, we investigated the different anticancer activities of, and considered resistance mechanisms to, TQ. MTT and clonogenic data showed TQ’s ability to suppress breast MDA-MB-468 and T-47D proliferation at lower concentrations compared to other cancer and non-transformed cell lines tested (GI50 values ≤ 1.5 µM). Flow-cytometric analyses revealed that TQ consistently induced MDA-MB-468 and T-47D cell-cycle perturbation, specifically inducing pre-G1 populations. In comparison, less sensitive breast MCF-7 and colon HCT-116 cells exhibited only transient increases in pre-G1 events. Annexin V/PI staining confirmed apoptosis induction in MDA-MB-468 and HCT-116 cells, which was continuous in the former and transient in the latter. Experiments revealed the role of reactive oxygen species (ROS) generation and aneuploidy induction in MDA-MB-468 cells within the first 24 h of treatment. The ROS-scavenger NAD(P)H dehydrogenase (quinone 1) (NQO1; DT-diaphorase) and glutathione (GSH) were implicated in resistance to TQ. Indeed, western blot analyses showed that NQO1 is expressed in all cell lines in this study, except those most sensitive to TQ-MDA-MB-468 and T-47D. Moreover, TQ treatment increased NQO1 expression in HCT-116 in a concentration-dependent fashion. Measurement of GSH activity in MDA-MB-468 and HCT-116 cells found that GSH is similarly active in both cell lines. Furthermore, GSH depletion rendered these cells more sensitive to TQ’s antiproliferative actions. Therefore, to bypass putative inactivation of the TQ semiquinone metabolite, the benzylamine analogue was designed and synthesised following modification of TQ’s carbon-3 atom. However, the structural modification negatively impacted potency against MDA-MB-468 cells. In conclusion, we disclose the following: (i) The anticancer activity of TQ may be a consequence of ROS generation and aneuploidy; (ii) Early GSH depletion could substantially enhance TQ’s anticancer activity; (iii) Benzylamine substitution at TQ’s carbon-3 failed to enhance anticancer activity.

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“…The cocrystal ligands DTQ for CDK2, and 13Q for P53-MDM2 complex were redocked to assure the validity of the docking parameters and methods to represent the position and orientation of the ligand detected in the crystal structure. The difference of RMSD value between cocrystal ligands to the original cocrystal ligand was <2Å which approved the accuracy of the docking protocols and parameters [56][57][58]. Figures 3 and 4 described the interaction of the most promising compound ( 16) with CDK2 and P53-MDM2 proteins compared to reference ligand (RL).…”

Section: Molecular Docking Studymentioning

confidence: 77%

Novel Melatonin Derivatives: Synthesis, Anticancer Evaluations and Molecular-Docking Study

et al. 2020

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Many studies mentioned that Melatonin considers an anti-cancer agent. So in this study, a lot of novel Melatonin derivatives incorporated different heterocyclic ring systems such as triazole, thiadiazole, tetrazole, thiazole, thiophene and pyrazole were synthesized. The synthesized compounds 5, 6, 8, 11, 15, 16 and 19 were evaluated as anti-cancer by using two human cancer cell lines, Breast cancer (MCF7) and colon cancer (HCT-116). The synthesized compounds showed a gradual decrease in the cell viability of the two cell lines. We also observed that compound 16 was the lowest IC50 and the highest cytotoxic effects against the two cancer cell lines. Furthermore, the molecular-docking study was employed to determine the possible mode of action of the synthesized compounds against proteins (CDK2 and P53-MDM2) which, were considered to be potential proteins involved in the pathogenesis of cancer. We observed that compound 16 was the best-docked ligand against the targeted proteins, as it displayed the lowest binding energies, critical hydrogen bonds, and hydrophobic interactions compared to other tested compounds.

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Thymoquinone-chemotherapeutic combinations: new regimen to combat cancer and cancer stem cells

Cited by 33 publications

References 128 publications

Thymoquinone Augments Methotrexate-Induced Apoptosis on Osteosarcoma Cells

Thymoquinone Augments Methotrexate-Induced Apoptosis on Osteosarcoma Cells

Concurrent Reactive Oxygen Species Generation and Aneuploidy Induction Contribute to Thymoquinone Anticancer Activity

Novel Melatonin Derivatives: Synthesis, Anticancer Evaluations and Molecular-Docking Study

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