Thymoquinone inhibits IL‐7‐induced tumor progression and metastatic invasion in prostate cancer cells by attenuating matrix metalloproteinase activity and Akt/NF‐κB signaling

Alshyarba, Mishari; Otifi, Hassan; Fayi, Majed Al; Dera, Ayed A.; Rajagopalan, Prasanna

doi:10.1002/bab.2062

Cited by 17 publications

(11 citation statements)

References 30 publications

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“…MMP-3 and MMP-7 drive the IL-7-induced tumor progression, migration, and invasion of DU-145 cells. Thymoquinone (Tq) treatment suppresses the activation of MMPs via IL-7/AKT/NF-κB signaling that inhibits IL-7-induced tumor progression and metastatic invasion in DU145 cells [82].…”

Section: Inflammatory Signaling and The Ecm Network Of The Tmementioning

confidence: 99%

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance

Zhong

Huang

Chen

et al. 2021

JCM

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Although castration-resistant prostate cancer (CRPC) as a whole, by its name, refers to the tumors that relapse and/or regrow independently of androgen after androgen deprivation therapy (ADT), untreated tumor, even in early-stage primary prostate cancer (PCa), contains androgen-independent (AI) PCa cells. The transformation of androgen-dependent (AD) PCa to AI PCa under ADT is a forced evolutionary process, in which the small group of AI PCa cells that exist in primary tumors has the unique opportunity to proliferate and expand selectively and dominantly, while some AD PCa cells that have escaped from ADT-induced death acquire the capability to survive in an androgen-depleted environment. The adaptation and reprogramming of both PCa cells and the tumor microenvironment (TME) under ADT make PCa much stronger than primary tumors so that, currently, there are no effective therapeutic methods available for the treatment of CRPC. Many mechanisms have been found to be related to the emergence and maintenance of PCa castration resistance; in this review, we focus on the role of inflammatory signaling in both PCa cells and the TME for the emergence and maintenance of CRPC and summarize the recent advances of therapeutic strategies that target inflammatory signaling for the treatment of CRPC.

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Section: Inflammatory Signaling and The Ecm Network Of The Tmementioning

confidence: 99%

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance

Zhong

Huang

Chen

et al. 2021

JCM

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“…[14] The anticancer effect of TQ has been reported in different types of cancers including prostate cancer, osteosarcoma, fibrosarcoma, myeloblastic leukemia, colorectal carcinoma, and lung cancer. [15][16][17][18] In our present study, the antioxidant, antiproliferative, and apoptosis-inducing effects of TQ were analyzed to explore its anticancer efficacy against B(a)P-induced lung cancer in mice.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(a)pyrene‐induced experimental lung cancer

Nithya

Rajasekaran

Vanitha

et al. 2022

J Biochem & Molecular Tox

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Several studies have suggested that increased consumption of phytochemicals is a comparatively easy and practical strategy to significantly decrease the incidence of cancer. In the present study, we have reported the protective effect of a natural compound, thymoquinone (TQ) against benzo(a)pyrene (B(a)P)‐induced lung carcinogenesis in Swiss albino mice. B(a)P (50 mg/kg body weight) was administered twice weekly for four successive weeks and left until 20 weeks to induce lung cancer in mice. TQ (20 mg/kg body weight) was given orally as a pretreatment and posttreatment drug to determine its chemopreventive and therapeutic effects. B(a)P‐induced lung cancer‐bearing animals displayed cachexia‐like symptoms along with an abnormal increase in lung weight and the activities of marker enzymes adenosine deaminase, aryl hydrocarbon hydroxylase, gamma‐glutamyl transpeptidase, 5′‐nucleotidase and lactate dehydrogenase; tumor marker carcinoembryonic antigen levels. Furthermore, B(a)P‐induced animals showed elevated levels of lipid peroxides with subsequent depletion in the antioxidant status and histological aberrations. These anomalies were accompanied by increased expressions of proliferating cell nuclear antigen and cyclin D1 in the lung sections derived from B(a)P‐induced animals. On TQ treatment, all the above alterations were returned to near normalcy. Furthermore, TQ administration in B(a)P‐induced animals downregulated phosphatidylinositol 3‐kinase/protein kinase B signaling pathway and induced apoptosis as evidenced by a decrease in cytochrome c, proapoptotic Bax, caspase‐3, and p53 with a parallel increase in antiapoptotic Bcl‐2. Our present results demonstrate the potential effectiveness of TQ as an antioxidant, antiproliferative, and apoptotic agent against B(a)P‐induced experimental lung tumorigenesis.

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“…13 TQ is one of the components extracted from Nigella sativa seeds and it has been reported to have antioxidant, 14 anti-inflammatory, 15 and anticancer effects. 16 Moreover, studies revealed that TQ could inhibit cancer cells growth and induce apoptosis in many malignancies such as breast, 17 lung, 18 colon, 19 pancreas, 20 prostate, 21 ovary cancers, 22 and leukemia. 23 However, along with its benefits, it showed inhibitory effects on CYP2C19, CYP2C9, CYP2D6, and CYP3A4, and it can cause herb-drug interactions.…”

Section: Introductionmentioning

confidence: 99%

Effect of thymoquinone on pharmacokinetics of 5-fluorouracil in rats and its effect on human cell line in vitro

2022

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Thymoquinone (TQ) is one of the components extracted from Nigella sativa seeds and has antioxidant, anti-inflammatory, and anticancer effects. We evaluated the effect of TQ on 5-fluorouracil (5-FU) pharmacokinetics (PK) in vivo and in vitro on human colorectal cancer cell line. Ten Adult male Wistar rats were assigned to two groups. TQ treated group received intraperitoneal TQ once daily for 14 consecutive days (5 mg/kg). Both groups received intraperitoneal 5-FU (50 mg/kg) on day 15 and blood samples were collected from retro-orbital plexus. The pharmacokinetics parameters were analyzed using high-performance liquid chromatography (HPLC). Moreover, various concentrations of 5-FU, TQ, and combination of 5-FU and TQ were added to the HT-29 cell line and cell viability was measured using 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetric assay. The maximum serum concentration ( Cmax), area under the curve (AUC), and time of maximum concentration ( Tmax) of 5-FU in TQ treated group were significantly increased approximately by 61, 60, and 24% compared to the control group, respectively. The combination of 5-FU with TQ (0.284 mM) showed a greater inhibitory effect on HT-29 cell growth compared to the alone 5-FU (0.027 and 0.055 mM) administration. TQ increases the AUC, Cmax, and Tmax of 5-FU and has a synergistic effect on the PK of 5-FU. Moreover, low concentration of TQ enhances the inhibitory effects of 5-FU on cell growth in colorectal cancer cell line. This synergistic effect might enhance the anticancer effects of low concentration of 5-FU, leading to drug dose reduction and reduced systemic toxicity of this chemotherapeutic agent.

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Thymoquinone inhibits IL‐7‐induced tumor progression and metastatic invasion in prostate cancer cells by attenuating matrix metalloproteinase activity and Akt/NF‐κB signaling

Cited by 17 publications

References 30 publications

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance

Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(a)pyrene‐induced experimental lung cancer

Effect of thymoquinone on pharmacokinetics of 5-fluorouracil in rats and its effect on human cell line in vitro

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