Thymoquinone In Combination Research Articles

Inactivation of Pseudomonas aeruginosa biofilms by thymoquinone in combination with nisin.

Pseudomonas aeruginosa is one of the most important foodborne pathogens that can persist in leafy green vegetables and subsequently produce biofilms. In this study, the synergistic effect of thymoquinone and nisin in reducing biofilm formation of P. aeruginosa on lettuce was evaluated, and their anti-virulence and anti-biofilm mechanisms were also investigated. At concentrations ranging from 0.5 to 2 mg/ml, thymoquinone inhibited the production of autoinducers and virulence factors, and enhanced the susceptibility of P. aeruginosa biofilms to nisin as evidenced by the scanning electron microscopy and confocal laser scanning microscopy. Integrated transcriptomics, metabolomics, and docking analyses indicated that thymoquinone treatment disrupted the quorum sensing (QS) system, altered cell membrane component, and down-regulated the expressions of genes related to virulence, efflux pump, and antioxidation. The changed membrane component and repressed efflux pump system enhanced membrane permeability and facilitated the entrance of nisin into cells, thus improving the susceptibility of biofilms to nisin. The dysfunctional QS and repressed antioxidant enzymes lead to the enhancement of oxidative stress. The enhanced oxidative stress disrupted energy metabolism and protein metabolism and ultimately attenuated the virulence and pathogenicity of P. aeruginosa PAO1. Our study indicated that thymoquinone has the potential to function as a QS-based agent to defend against foodborne pathogens in combination with nisin.

The Antimicrobial and Toxicity Influence of Six Carrier Oils on Essential Oil Compounds

Essential oil compounds have been identified as alternative antimicrobials; however, their use is limited due to their toxicity on human lymphocytes, skin, and reproduction. Carrier oils can reduce the toxicity of essential oils, which raises the question as to whether such activity would extend to the essential oil compounds. Thus, this study aimed to investigate the antimicrobial and toxicity activity of essential oil compounds in combination with carrier oils. The antimicrobial properties of the essential oil compounds, alone and in combination with carrier oils, were determined using the broth microdilution assay. The toxicity was determined using the brine shrimp lethality assay. Antimicrobial synergy (ΣFIC ≤ 0.50) occurred in 3% of the samples when tested against the ESKAPE pathogens. The compound thymoquinone in combination with the carrier oil Prunus armeniaca demonstrated broad-spectrum synergistic activity and a selectivity index above four, highlighting this combination as the most favorable. The carrier oils reduced the toxicity of several compounds, with Calendula officinalis and P. armeniaca carrier oils being responsible for the majority of the reduced toxicity observed. This study provides insight into the interactions that may occur when adding a carrier oil to essential oil compounds.

EFFECT OF THYMOQUINONE IN COMBINATION WITH NIVOLUMAB ON EXPERIMENTAL RENAL CELL CANCER MODELS

Objectives: Thymoquinone a bioactive component extracted from the seeds of Nigella sativa, has been proved to have antiinflammatory, antioxidant properties anti antitumor efficiency against breast, prostate, bladder, and renal cell cancer. We aimed to investigate the synergistic cytotoxic and apoptotic effects of thymoquinone in combination with nivolumab, an immuno-control inhibitor, and its mechanism in renal cell cancer models. Materials and Methods: In vitro studies: Caki-1 and Renca renal cancer cell lines with mononuclear cells were cocultured and thymoquinone and nivolumab effect were analyzed by MTT and Annexin V + PI. In vivo studies: Renal cell cancer model was provided by subcutaneous injection of RENCA cells to C57BL/6, male, 8 weeks old mice in four groups. Control group, thymoquinone (1,4,7,14days,20mg/kgIP), nivolumab administered (1,6,13days10mg/ kgIP), thymoquinone and nivolumab. Seven animals was randomized in each experimental group. Apoptosis, necrosis, CD4,CD8,C20,CD34,CD31,VEGF-A by immunohistochemistry, FGFR-1,PDGFRbeta,VEGFR-2,c-kit,RET,c-Met,AXL,Flt-3,TIE2, ICAM-1,VCAM-1 and E-selectin mRNA levels by quantitative real-timePCR were evaluated on tumor tissue. Liver, kidney, brain, lung and heart tissues was evaluated for side effects. Plasma biochemistry tests were performed. Statistical analysis was be performed with Mann-Whitney U test with p <0.05 value. Results: Thymoquinone showed antitumor effect in vitro and in vivo. It also showed increase in immune cell death of nivolumab. Tumor tissue showed prominent necrosis or complete response to therapy in combination group. Conclusions: We conclude that thymoquinone has antitumor effect on renal cell carcinoma and increases the effect of nivolumab immune, cell death effects. Besides, it does not have side effect on other organs whether alone or in combination. 

Abstract PO-011: Targeting colorectal cancer stem/progenitor cells with a combination of ionizing radiation and thymoquinone

Abstract Introduction: Radiotherapy is a standard neo-adjuvant therapy for cancer treatment, the success of which is limited by the resistance of cancer stem cells (CSCs) to therapy in addition to the deleterious effects of ionizing radiation (IR) to surrounding normal tissues. Despite the anticancer efficacy of combining IR with standard chemotherapeutic drugs, such treatments have shown great toxicity to normal cells. Thus, recent therapeutic strategies have aimed to combine IR with natural compounds that could radiosensitize and target cancer cells while sparing healthy tissues. The plant-derived compound Thymoquinone (TQ) has limited toxicity and is known to exert a radio-potentiating role in breast cancer and head and neck squamous cell carcinomas. Yet, no studies have investigated the antitumor effect of TQ in combination with IR on CSCs. Here, we studied the effect of TQ alone or in combination with IR on CSCs derived from different human colorectal cancer cell lines. Methods: MTT and trypan blue exclusion assays were used to study the effect of TQ and IR on proliferation and viability of HCT116 p53+/+, HCT116 p53−/−, and HT-29 p53+/− human colorectal cancer cell lines. The effect of TQ and IR on the long-term survival of different CRC cell lines was investigated by colony formation assay. Three-dimensional (3D) spheroid models derived from radiation resistant cells were used to enrich for stem/progenitor cells and study effects on CSCs self-renewal capacity. Results: IR doses of 1 or 2 Gray (Gy) significantly reduced the proliferation of HCT116 p53+/+ cells at 48 hours post IR. The antiproliferative effect of IR (2 Gy) on HCT116 p53−/− and HCT116 p53+/+ cells was significantly enhanced at 48 hours when combined with TQ at doses as low as 20 µM and 40 µM, respectively. While treatment of HCT116 p53+/+, HCT116 p53−/−, and HT-29 cells with 2 Gy IR or 10 µM TQ alone showed no significant inhibition on cell viability at 48 hours, combining the same doses of TQ and IR showed an enhanced and significant effect on cell viability when compared to TQ alone. Interestingly, combination treatment induced a more pronounced reduction in colony formation ability than either treatment alone at doses as low as 10 µM TQ. Of relevance to 3D systems, the combination of 3 µM TQ and 2 Gy IR significantly inhibited the self-renewal capacity of radiation resistant colonospheres derived from HT-29 cells at generation 1 (G1). Conclusion: Our study shows that the combination of IR with TQ appears to be a promising therapeutic strategy for eradicating radioresistant colorectal cancer cells and stem/progenitor cells. Citation Format: Samar Al Bitar, Farah Ballout, Wassim Abou-Kheir, Hala Gali-Muhtasib. Targeting colorectal cancer stem/progenitor cells with a combination of ionizing radiation and thymoquinone [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-011.

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

Cancer is a worldwide disease that causes millions of cases of mortality and morbidity. The major problem associated with the cancer is its resistance to conventional therapy and a high relapse rate. The use of chemotherapy to treat cancer began at the start of the twentieth century with attempts to control cancer. In time advance, many cancer chemotherapeutic agents have been developed for cancer treatment with different mechanisms of action including the alkylating agents, antimetabolites, antimicrotubule, topoisomerase inhibitors, and cytotoxic antibiotics, all of which have toxic effects toward normal cells in the body. Here, we reviewed chemotherapeutics' anticancer role potentiation and safety by thymoquinone (TQ) alone or in combination with the most common therapeutic drugs. Our search was done through PubMed, Science Direct, Springer Link, Taylor & Francis Online, Wiley Online Library, Nature publication group, SAGE Journals, and Web of Science databases. We recognized that TQ-chemotherapeutics combination increased chemo-modulation to the anticancer effect of different chemotherapeutics and protected the normal body cells from the toxic injuries that are induced by chemotherapeutics based on its antioxidant power. Moreover, the current study investigates the possible combinatory effect of TQ and chemotherapeutics to control cancer stem cells through molecular docking targeting of wingless/integrated (Wnt) and Hedgehog (Hh). We found that TQ modulates the Wnt and Hh pathways, by binding with tankyrase-2 and smoothened 7TM receptor, respectively, more efficiently than most chemotherapeutics drugs, while methotrexate showed high-binding affinity compared with TQ. Therefore, we encourage researchers to investigate the chemo-modulatory potential and protective effects of TQ in combination with chemotherapeutics for either cancer or cancer stem cell treatment.

P11.55 Thymoquinone enhances the sensitivity of B16-F10 melanoma cell line to Gamma Knife radiosurgery

Abstract BACKGROUND Melanoma patients with brain metastasis have poor prognosis. Gamma Knife radiosurgery (GKR) is an effective treatment to control brain metastasis from melanoma. Thymoquinone (TQ) has gained attention as a potential therapeutic option due to its anti-tumor effects on various cancers. The aim of the study was to invetsigate the effect of GKR in B16-F10 melanoma cells in vitro and in established intracerebral melanoma model in mice in vivo, and the sensitizing efficacy of TQ towards GKR. MATERIAL AND METHODS Effects of GKR and combination treatment of GKR and TQ were studied on B16-F10 melanoma cells via analyzing cytotoxicty by adenosine triphosphate (ATP) assay; apoptosis induction by acridine orange staining and genotoxicity by comet assay. Expression of STAT3, p-STAT3 (Tyr705) and apoptotic pathway proteins was investigated by western blot analysis. Enzyme Linked Immunosorbent Assay (ELISA) was performed to assess the expression of inflammatory cytokines. Also survival was evaluated in mice with brain tumor after GKR and its combination treatment with TQ. RESULTS The effects of GKR on cytotoxicity, apoptosis and genotxicity were significantly enhanced by TQ on B16-F10 melanoma cells. GKR induced apoptosis through inhibition of p-STAT3 expression, which subsequently regulated pro- and anti-apoptotic proteins such as caspase-3, Bax, Bcl-2, survivin. Combination TQ with GKR irradiation enhanced the apoptotic effect of GKR irradiation. Furthermore, GKR decreased the levels of tumor-related inflammatory cytokines on B16-F10 melanoma cells. This effect was more pronounced when TQ was added to GKR irradiation. GKR with 15 Gy improved the survival of mice with intracerebral melanoma compared to untreated mice. Although, the additive effect of TQ in combination with GKR irradiation on B16-F10 melanoma cells in vitro, TQ did not add any significant survival benefit to GKR treatment in mice with intracerebral melanoma. CONCLUSION Our findings indicate that TQ would be a potential therapeutic and sensitizing agent in addition to GKR to enhance the anti-tumor effect of irradiation. Further studies are required to support our findings.

Evaluation of DNA interaction, genotoxicity and oxidative stress induced by iron oxide nanoparticles both in vitro and in vivo: attenuation by thymoquinone

Iron oxide nanoparticles (IONPs) are known to induce cytotoxicity in various cancer cell lines through the generation of reactive oxygen species (ROS). However, the studies on its potential to induce toxicity in normal cell lines and in vivo system are limited and ambiguity still exists. Additionally, small molecules are known to interact with the DNA and cause damage to the DNA. The present study is designed to evaluate the potential interaction of IONPs with DNA along with their other toxicological effects and subsequent attenuation by thymoquinone both in vitro (primary lymphocytes) and in vivo (Wistar rats). IONPs were characterized by TEM, SEM-EDS, and XRD. The results from DNA interaction studies showed that IONPs formed a complex with DNA and also got intercalated between the base pairs of the DNA. The decrease in percent cell viability of rat’s lymphocytes was observed along with an increase in ROS generation in a dose-dependent manner (50, 100, 200, 400 and 800 μg/ml of IONPs). The genetic damage in in vivo might be due to the generation of ROS as depletion in anti-enzymatic activity was observed along with an increase in lipid peroxidation in a dose–dependent manner (25, 50, 100 mg/kg of IONPs). Interestingly, supplementation of thymoquinone in combination with IONPs has significantly (P < 0.05) attenuated the genetic and oxidative damage in a dose-dependent manner both in vitro and in vivo. It can be concluded that thymoquinone has the potential to attenuate the oxidative stress and genetic toxicity in vitro and in vivo.

Abstract 1049: Combinatorial effects of thymoquinone on the anticancer activity of doxorubicin in adult T-cell leukemia

Abstract Doxorubicin (Dox) is a clinically approved drug which suffers from drug resistance and cardiotoxicity. Recent studies have shown that thymoquinone (TQ) in combination with Dox can reduce Dox toxic side effects in vitro as well as in vivo. Both TQ and Dox have shown promising anticancer effects against aggressive adult T-cell leukemia (ATL), however, the anticancer potential of TQ and Dox combination treatment has never been tested against ATL. We hypothesized that co-treatment with TQ could enable the use of lower doses of Dox to achieve similar or enhanced anticancer activity. The effects of TQ and Dox combination on cell death and cell cycle were evaluated by trypan blue and propidium iodide. TUNEL assay was used to investigate the mode of cell death. The levels of reactive species (ROS) were determined using DCFH assay, and mitochondrial membrane potential was measured by rhodamine assay. The regulation of key proteins involved in cell cycle regulation and cell death was determined by Western blot. The results reveal that the human T-lymphotropic virus (HTLV-1) positive HuT-102 cells are more resistant to treatment with Dox alone, than the HTLV-1 negative Jurkat cells. However, treatment with high doses of TQ and low doses of Dox simultaneously, enhances cell death in both cancer cell lines as compared to treatment with Dox alone. TUNEL assay on Jurkat and HuT-102 cells further indicated that the combination of TQ and Dox caused cell death by apoptosis. An increase in ROS production was noted in response to treatment with TQ alone and with TQ and Dox combination in both Jurkat and HuT-102 cells. The oxidative stress; however, was only shown to play a role in the disruption of the mitochondria of Jurkat cells. Similarly, caspase activation was involved in the disruption of the mitochondria of Jurkat cells. The expression levels of key regulatory proteins were modulated in response to treatment with the combination. In conclusion, the combination of TQ and Dox effectively inhibits ATL leukemic cancer cell growth at lower doses of Dox which can potentially lower the side effects of the drug. In vivo studies are still warranted to assess the adjuvant chemotherapeutic potential of TQ in combination with Dox. Citation Format: Hala Gali-Muhtasib, Isabelle Fakhoury, Maamoun Fatfat, Rasha Mismar, Regine Schneider-Stock. Combinatorial effects of thymoquinone on the anticancer activity of doxorubicin in adult T-cell leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1049. doi:10.1158/1538-7445.AM2017-1049

An active principle of Nigella sativa L., thymoquinone, showing significant antimicrobial activity against anaerobic bacteria.

Thymoquinone (TQ) is the major active principle of Nigella sativa seed (black seed) and is known to control many fungi, bacteria, and some viruses. However, the activity of TQ against anaerobic bacteria is not well demonstrated. Anaerobic bacteria can cause severe infections, including diarrhea, aspiration pneumonia, and brain abscess, particularly in immunodeficient individuals. The present study aimed to investigate the in vitro antimicrobial activity of TQ against some anaerobic pathogens in comparison to metronidazole. Standard, ATCC, strains of four anaerobic bacteria (Clostridium difficile, Clostridium perfringens, Bacteroides fragilis, and Bacteroides thetaiotaomicron), were initially isolated on special Brucella agar base (with hemin and vitamin K). Then, minimum inhibitory concentrations (MICs) of TQ and metronidazole were determined against these anaerobes when grown in Brucella agar, using serial agar dilution method according to the recommended guidelines for anaerobic organisms instructed by the Clinical and Laboratory Standards Institute. TQ showed a significant antimicrobial activity against anaerobic bacteria although much weaker than metronidazole. MICs of TQ and metronidazole against various anaerobic human pathogens tested were found to be between 10-160 mg/L and 0.19-6.25 mg/L, respectively. TQ controlled the anaerobic human pathogenic bacteria, which supports the use of N. sativa in the treatment of diarrhea in folk medicine. Further investigations are in need for determination of the synergistic effect of TQ in combination with metronidazole and the activity of derivatives of TQ against anaerobic infections.

Thymoquinone Pretreatment Overcomes the Insensitivity and Potentiates the Antitumor Effect of Gemcitabine Through Abrogation of Notch1, PI3K/Akt/mTOR Regulated Signaling Pathways in Pancreatic Cancer.

The gemcitabine-insensitivity remains the main challenge for pancreatic cancer treatment. Thymoquinone, the predominant bioactive ingredient of Nigella sativa, has been shown to possess promising anti-cancer and chemo-sensitizing effects on pancreatic cancer, however, its meticulous mechanism is still indistinct. The objective of the present study was to investigate the potency of thymoquinone in combination with gemcitabine in inducing apoptosis and preventing the development of gemcitabine-insensitivity in pancreatic cancer cells. The anti-tumor effects of thymoquinone and gemcitabine were analyzed via evaluation of alterations of cell viability, tumor weight, apoptosis-related proteins, caspase-3, -9 activities and NF-κB DNA binding activity in pancreatic cancer cells in vitro and PANC-1 cells orthotopic xenograft in vivo. Thymoquinone pretreatment following gemcitabine treatment synergistically caused an increase in pancreatic cancer cells apoptosis and tumor growth inhibition both in vitro and in vivo. The novel combinational regimen also contributes to alterations of multiple molecular signaling targets, such as the suppression of Notch1, NICD accompanying with up-regulation of PTEN, the inactivation of Akt/mTOR/S6 signaling pathways, and the suppression of phosphorylation and nuclear translocation of p65 induced by TNF-α. Thymoquinone pretreatment and gemcitabine also induced down-regulation of anti-apoptotic Bcl-2, Bcl-xL, XIAP and up-regulation and activation of pro-apoptotic molecules including Caspase-3, Caspase-9, Bax and increased release of cytochrome c. This novel modality of thymoquinone pretreatment can enhance the anti-cancer activity of gemcitabine and may be a promising option in the treatment of pancreatic cancer.

Synergistic combination of gemcitabine and dietary molecule induces apoptosis in pancreatic cancer cells and down regulates PKM2 expression.

Gemcitabine, an effective agent in treatment of cancer of pancreas, has undergone failures in many instances after multiple cycles of therapy due to emergence of drug resistance. Combination of dietary compounds with clinically validated drugs has emerged as an effective therapeutic approach to treat pancreatic tumors, refractory to gemcitabine therapy. In order to optimize a possible synergistic combination of Gemcitabine (GCB) with dietary molecules, Betuilnic acid (BA) and Thymoquinone (TQ), stand-alone IC50 dose of GCB, BA and TQ was calculated for pancreatic cancer cell lines. Fixed IC50 dose ratio of the dietary molecules in combination with reduced IC50 dose of GCB was tested on GCB resistant PANC-1 and sensitive MIA PaCa-2 cells for synergism, additive response and antagonism, using calcusyn. Combination index (CI) revealed that pre-treatment of BA and TQ along with GCB synergistically inhibited the cancer cell proliferation in in-vitro experiments. Pyruvate kinase (PK) M2 isoform, a promising target involved in cancer cell metabolism, showed down-regulation in presence of TQ or BA in combination with GCB. GCB with BA acted preferentially on tumor mitochondria and triggered mitochondrial permeability transition. Pre-exposure of the cell lines, MIA PaCa-2 and PANC-1, to TQ in combination with GCB induced apoptosis. Thus, the effectiveness of BA or TQ in combination with GCB to inhibit cell proliferation, induce apoptosis and down-regulate the expression of PKM2, reflects promise in pancreatic cancer treatment.

Radiosensitization in human breast carcinoma cells by thymoquinone: role of cell cycle and apoptosis

TQ (thymoquinone), the bioactive constituent of black seed (Nigella sativa), has been shown to inhibit the growth of various human cancers both in vitro and in vivo. This study reports the radiosensitizing effect of TQ on human breast carcinoma cells (MCF7 and T47D). TQ in combination with single dose of ionizing radiation (2.5 Gy) was found to exert supra-additive cytotoxic effects on both the carcinomas as measured by cell proliferation and colony-formation assays. Annexin V binding and FACS analysis revealed the role of enhanced apoptosis and cell cycle modulation in the mechanism of TQ-mediated radiosensitization, thus supporting TQ as an adjuvant for preclinical testing in cancer chemo-radiotherapy.

Abstract 4225: Thymoquinone induces cell death in glioblasotma cell through production of reactive oxygen species and induction of DNA damage

Abstract Glioblastoma is the most aggressive and common type of brain tumors in humans. Surgical resection followed by radiation and chemotherapy is the current standard treatment; however, due to up-regulation of several survival pathways, tumor recurrence is quite common with a median survival of 12 to 15 months. Therefore, there is an urge for more effective therapeutic strategies for the treatment of glioblastoma. Over years the use of natural compounds as anticancer agents acquired great importance. Thymoquinone (TQ) is the bioactive component of the volatile oil extracted from the black seed, Nigella sativa. TQ has shown anti-oxidant, anti-inflammatory, and anti-neoplastic actions in in-vitro and in-vivo models with a selective cytotoxicity for human cancer cells compared to several normal cells. Here, we report that TQ greatly inhibited cell proliferation of radioresistant glioma cells (U87 and T98) in a concentration-dependent manner. Moreover, TQ mediated reactive oxygen species-induced DNA breaks in glioma cells, as detected by the appearance of post-DNA damage sensitive marker γH2AX. Our results also showed that TQ up-regulated p53 in U87 cells while down-regulated phospho-Akt in T98 cells in a dose-dependent manner. Current investigations are ongoing to use TQ in combination with ionizing radiation as a promising modality to overcome resistance, thereby reducing ionizing radiation doses used for glioma treatment. This work was supported by NIH grants CA93413, ES2388 and ES12991 to A. A. W. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4225. doi:10.1158/1538-7445.AM2011-4225

Abstract B154: Thymoquinone causes mitochondrial membrane disruption and potentiates chemotherapeutic drug- and radiation-induced cytotoxicity in breast cancer cells

Abstract Thymoquinone, which is the active constituent of the volatile oil extracted from black caraway seeds (Nigella sativa), has been reported to have antiinflammatory, antioxidant, and antineoplastic activities in vitro and in vivo. In this study we explored the mechanism by which thymoquinone inhibits breast cancer cell growth, as well as the potential of using thymoquinone in combination with conventional chemotherapeutic drugs or radiation therapy. Cytofluorimetric analysis of Oregon Green 488-stained MDA-MB-231 and MDA-MB-468 breast cancer cells following thymoquinone treatment demonstrated inhibition of cell proliferation. Colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays performed on MDA-MB-231, MDA-MB-468, and T-47D breast cancer cells after 24, 48, and 72 h treatment with thymoquinone (0.5–10 µM) showed a time- and dose-dependent cytotoxic effect, while untransformed human mammary epithelial cells were not adversely affected by thymoquinone. Longer exposure (144 h) to lower doses of thymoquinone (0.25–1 µM) was also cytotoxic for breast carcinoma cells. Importantly, staining of thymoquinone-treated breast cancer cells with annexin-V-FLUOS/propidium iodide indicated that cell death was by apoptosis. Western blot analysis of thymoquinone-treated breast cancer cells revealed increased cytosolic cytochrome c and PARP cleavage, which suggested induction of the mitochondrial pathway of apoptosis. However, broad spectrum caspase inhibitors (Bod-D and z-VAD-fmk) did not prevent thymoquinone-induced cytotoxicity, implying caspase-independent cell death. Thymoquinone treatment also sensitized breast cancer cells to γ-radiation and the conventional chemotherapeutic agents docetaxel and cisplatin. We conclude that thymoquinone caused caspase-independent apoptosis in breast cancer cells that involved the loss of mitochondrial membrane integrity. Furthermore, the ability of thymoquinone to potentiate the cytotoxic effects of chemotherapeutic drugs and -radiation may have application in a clinical setting. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B154.