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

Abstract

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.

Azadirachtin Attenuates Carcinogen Benzo(a) Pyrene-Induced DNA Damage, Cell Cycle Arrest, Apoptosis, Inflammatory, Metabolic, and Oxidative Stress in HepG2 Cells

“…A reduction in mitochondrial ROS with AZD treatment was confirmed using a ROS-sensitive, mitochondrial-specific fluorogenic probe, CM-H2XRos (Mito Tracker ® Red), which specifically measures the intracellular production of hydrogen peroxide. Studies have shown the increased cellular content of MDA after treatment with B(a)P, indicating increased oxidative stress [6,39,[41][42][43]. Our study also confirmed increased MDA levels after B(a)P treatment, which were alleviated in the presence of AZD.…”

Thymoquinone: A Promising Therapeutic Agent for the Treatment of Colorectal Cancer

“…Particular attention is currently being paid to research into the anticancer effects of TQ. Thymoquinone has anticancer properties that have been confirmed in preclinical studies of many types of cancer, including ovarian, colon, laryngeal, breast, leukemia, lung and osteosarcoma [67][68][69][70][71][72][73][74][75][76]. Currently, there is only one clinical trial evaluating the chemopreventive effect of thymoquinone on potentially malignant oral lesions in the clinicaltrials.gov database (accessed 14 November 2023).…”

Synthesis and Characterization of Thymoquinone‐Oxime (TQ‐Ox) from Thymoquinone and Evaluation of its Cytotoxic, Genotoxic, and Apoptotic Potential in Lung Cancer Cells (A549) in vitro

“…This is supported by experimental studies emphasizing the robust molecular interactions of oximes. [11] The literature contains many studies examining TQ's potential as an anticancer agent in vitro and in vivo; [12][13][14][15][16] however, there is only one study on ovarian cancer related to TQ-oxime (TQÀ Ox). [17] Notably, our study marks the first exploration of TQÀ Ox's effects on a lung cancer cell line.…”