Thymoquinone loaded calcium alginate and polyvinyl alcohol carrier inhibits the 7,12‐dimethylbenz[a]anthracene‐induced hamster oral cancer via the down‐regulation of PI3K/AKT/mTOR signaling pathways

Abstract

Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12‐Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF‐κBp50, NF‐κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT‐PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca‐alg‐PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca‐alg‐PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF‐κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca‐alg‐PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti‐invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca‐alg‐PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

Evaluation of differential white blood cell count and cheek pouch epithelium in 7,12-dimethylbenza[a]anthracene hamster carcinogenesis model, managed with three phytochemicals

“…In addition, TQ was suggested to express an antioxidant anti-inflammatory effect and enhance the detoxification processes [29,30]. Thymoquinone was reported to have different beneficial effects, such as; immunoregulatory [31], antioxidant [32], antidiabetic [33], anti-inflammatory [34], pain relieving [35], blood pressure regulatory [36], gastro protecting [37], renal protecting [38], and anti-malignancy [31,39,40].…”

Naturally-Occurring Bioactives in Oral Cancer: Preclinical and Clinical Studies, Bottlenecks and Future Directions

“…Abdelfadil et al [101], in 2013, demonstrated that thymoquinone induces apoptosis by downregulating the p38MAPK pathway in chemically induced oral squamous cell carcinoma (T28). Pu et al [102], in 2021, showed that thymoquinone down-regulated the inflammatory and PI3K/AKT/mTOR signaling pathway in orally treated 7,12-dimethylbenz[a]anthracene (DMBA)stimulated hamster oral tumor. In addition to being effective as a treatment for cancer, thymoquinone is also effective as a chemopreventive agent.…”

The applications of polysaccharides in dentistry

“…However, the biopolymer inhibits the growth of oral cancer cells and has good antibacterial activity against Escherichia coli and Staphylococcus aureus and, thus, is suitable for topical wound care and periodontitis and oral cancer treatment (Chiaoprakobkij et al, 2020). TQ/Ca-alg-PVA, a product of loading with calcium alginate and polyvinyl alcohol onto thymoquinone (TQ), inhibits early-stage oral cancer in 7,12-Dimethylbenz [a]anthracene (DMBA) painted hamster by downregulating the expression of NF-κB p50/p65, and PI3K/ AKT/mTOR mRNA (Pu et al, 2021). In summary, natural polysaccharides can achieve precise treatment and reduce the drug resistance of oral cancer.…”