Thymoquinone Augments Cyclophosphamide-Mediated Inhibition of Cell Proliferation in Breast Cancer Cells

Khan, Arif; Aldebasy, Yousef H; Alsuhaibani, Sultan A.; Khan, Masood Alam

doi:10.31557/apjcp.2019.20.4.1153

Cited by 29 publications

(16 citation statements)

References 31 publications

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“…As a result, we observed that TQ could synergistically improve tumor suppressive activities of DDP and DOX against HepG2 and SMMC-7721 cells, while the combinatorial treatments, especially TQ and DOX, showed low toxicity to normal liver HL-7702 cells. Consistent with our results, a recent study demonstrated that TQ could significantly potentiate the anti-cancer activity of cyclophosphamide against breast cancer cells ( Khan et al., 2019 ). Furthermore, we found that the cotreatment could induce more pronounced apoptosis of HCC cells than that of normal liver cells, suggesting that TQ exerted its cancer cell-inhibitory and normal cell-protective activities in these studies.…”

Section: Discussionsupporting

confidence: 93%

Thymoquinone Selectively Induces Hepatocellular Carcinoma Cell Apoptosis in Synergism With Clinical Therapeutics and Dependence of p53 Status

Jehan

Chen

et al. 2020

Front. Pharmacol.

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Thymoquinone (TQ) is a natural compound extracted from the black seeds of Nigella sativa Linn. belonging to the Ranunculaceae family. TQ exhibits anti-inflammatory and antineoplastic activities against various cancers. Many therapeutics in hepatocellular carcinoma (HCC) treatments, such as doxorubicin (DOX) and cisplatin (DDP), exhibit considerable side effects on patients. We investigated cytotoxic effects of TQ, alone or in combination with DDP and DOX to HCC cells. TQ exhibited selective killing to HCC HepG2 and SMMC-7721 cells, but relatively low toxicity to normal liver HL-7702 cells. Importantly, when used with DOX or DDP, TQ showed synergistic inhibition of HCC cells, but not HL-7702 cells. We also discovered that Hep3B cells with a p53 null status were more sensitive to TQ than HepG2 and SMMC-7721 cells harboring wild type p53. Consistently, shRNAmediated p53 silencing in HepG2 cells dramatically enhanced TQ-induced apoptosis, measured by caspase 3 and PARP cleavage. Furthermore, TQ-stimulated increase of reactive oxygen species (ROS) in p53-depleted cells was more pronounced than that in cells with intact p53. In summary, we discovered that TQ synergistically improves the anti-cancer activity of DOX and DDP, and loss of p53 sensitizes HCC cells to TQ-induced apoptosis.

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Section: Discussionsupporting

confidence: 93%

Thymoquinone Selectively Induces Hepatocellular Carcinoma Cell Apoptosis in Synergism With Clinical Therapeutics and Dependence of p53 Status

Jehan

Chen

et al. 2020

Front. Pharmacol.

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“…To combat PCa, combination therapy with a PI3K/AKT inhibitor can be regarded as horizontal blockade [34]. In breast [35] and gastric cancers [36], TQ inhibits the PI3K/AKT pathway by downregulating the phosphorylation of AKT and upregulating PTEN. In addition, DTX is a candidate for inhibition of the PI3K/AKT pathway.…”

Section: Discussionmentioning

confidence: 99%

Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway

Singh

Apata

Gordetsky

et al. 2019

Cancers

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Toxicity and the development of resistance by cancer cells are impediments for docetaxel (DTX), a primary drug for treating prostate cancer (PCa). Since the combination of DTX with natural compounds can increase its effectiveness by reducing its toxic concentrations, we evaluated a combination of thymoquinone (TQ) with DTX and determined its cytotoxicity against PCa cells (DU145 and C4-2B). This combination, in a concentration-dependent manner, resulted in synergistic cytotoxicity and apoptosis in comparison to either DTX or TQ alone. In addition, inhibition of cell survival pathways by PI3K/AKT inhibitors conferred sensitivity of DU145 and C4-2B cells to the combination as compared to the individual drugs. Moreover, the combined drugs (DTX+TQ) with inhibitors of PI3K/AKT increased the expression of pro-apoptotic markers (BAX and BID) along with caspase-3, PARP and decreased expression of the anti-apoptotic marker, BCL-XL. These data show that, for PCa cells, the cytotoxic effect of the DTX and TQ combination correlates with a block of the PI3K/AKT signaling pathway. These findings indicate that the combination of DTX and TQ, by blocking of the PI3K/AKT pathway, will improve the survival rate and quality of life of PCa patients.

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“…16 In addition, synergistic therapeutic effects were elicited when TQ was given in combination with other chemotherapeutic agents. 8,[17][18][19][20][21] The anticancer properties are mostly attributed to its antioxidant properties with pieces of evidence pointing towards its interference with specific cancer signaling pathways such as the MAPK, PI3-mTOR, JAK-STAT3 and NF-κB. [22][23][24][25] Poly lactic-co-glycolic acid (PLGA) is a FDA approved polymer known for its biomedical applications in drug delivery due to its versatility, biodegradability, and biocompatibility.…”

Section: Introductionmentioning

confidence: 99%

<p>Formulation, Cellular Uptake and Cytotoxicity of Thymoquinone-Loaded PLGA Nanoparticles in Malignant Melanoma Cancer Cells</p>

Ibrahim

Rosli

Doolaanea

2020

IJN

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Introduction: Thymoquinone (TQ) is the main active compound extracted from Nigella sativa a traditional herb with wide therapeutic applications and recognizable anticancer properties. This study aimed to formulate and characterize TQ-nanoparticles using PLGA as a biocompatible coating material (TQ-PLGA NPs) with the evaluation of its therapeutic properties in human melanoma cancer cells. Methods: The TQ-PLGA NPs were prepared and characterized for size, zeta potential, encapsulation efficiency, and release profile. Results: The particle size was 147.2 nm, with 22.1 positive zeta potential and 96.8% encapsulation efficiency. The NPs released 45.6% of the encapsulated TQ within 3 h followed by characteristic sustained release over 7 days with a total of 69.7% cumulative release. TQ-PLGA NPs were taken up effectively by the cells in a time-dependent manner up to 24 h. Higher cell toxicity was determined within the first 24 h in melanoma cells due to the rapid release of TQ from the NPs and its low stability in the cell culture media. Conclusion: TQ-PLGA NPs is a potential anticancer agent taking advantage of the sustained release and tailored size that allows accumulation in the cancer tissue by the enhanced permeability and retention effect. However, stability problems of the active ingredient were address in this study and requires further investigation.

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Thymoquinone Augments Cyclophosphamide-Mediated Inhibition of Cell Proliferation in Breast Cancer Cells

Cited by 29 publications

References 31 publications

Thymoquinone Selectively Induces Hepatocellular Carcinoma Cell Apoptosis in Synergism With Clinical Therapeutics and Dependence of p53 Status

Thymoquinone Selectively Induces Hepatocellular Carcinoma Cell Apoptosis in Synergism With Clinical Therapeutics and Dependence of p53 Status

Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway

<p>Formulation, Cellular Uptake and Cytotoxicity of Thymoquinone-Loaded PLGA Nanoparticles in Malignant Melanoma Cancer Cells</p>

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