Molecular evaluation of the chemotherapeutic effect of thymoquinone loaded on gold nanoparticles through expression of DNA repair enzymes in induced oral squamous cell carcinoma

Abstract

Introduction: Different types of DNA damages occur during the induced oral carcinogenesis, which can be eliminated through several DNA repair pathways. XRCC1 and ERCC1 are the main repair enzymes involved in repair of oral squamous cell carcinoma. A combination of thymoquinone with gold nanoparticles as a novel chemotherapeutic modality is the aim of the present work against chemically induced SCC in the classic model of HBP/DMBA carcinogenesis. Materials and methods: One hundred male Syrian golden hamsters were divided into: Group A: Ten animals (negative control), group B: Ten animals (positive control) painted with DMBA only 3times / week/ 12weeks. The rest of animals were painted with DMBA (3times / week/ 12weeks) then painted and injected intraperitoneal with TQ only, 0.01mg/kg TQ-GNps, 0.001mg/kg TQ-GNps or GNps only for 6-and 12-weeks, intervals. By end of the experiment, both pouches from all groups were surgically excised, fresh samples from each pouch were processed for RT-PCR technique. The rest of the pouches were fixed and processed for H&E evaluation. Results: Loading of thymoquinone on gold nanoparticles was promising chemotherapeutic combination, through regression of well-differentiated SCC (positive control) to dysplasia and enhanced expression of the studied DNA repair enzymes compared to either thymoquinone or gold nanoparticles groups. Conclusion:Loading of TQ on GNps revealed superior effect over the use of TQ only or GNps only in regression of tumors and increased expression of DNA repair enzymes.

Anticancer effects of thymoquinone in head and neck squamous cell carcinoma: A scoping review

“…Previous studies have shown that TQ impacts the oxidative stress environment of cancer cells, which may contribute to its chemoprevention and cytotoxicity in SCC 5,6,12,16 . As early as 1999, Badary et al investigated the effects of TQ on benzo(a)pyrene (BP)‐induced forestomach squamous cell tumors in mice 12 .…”

“…DNA repair enzymes such as XRCC1 are therefore integral to mitigating oxidative stress and subsequent carcinogenesis 77 . Amer et al's work in DMBA‐induced buccal pouch SCC in Syrian golden hamsters demonstrated that topical and intraperitoneal injection of TQ‐GNps resulted in cytotoxicity associated with an increase in mRNA and protein expression of XRCC1 5,6 …”

“…76 Previous studies have shown that TQ impacts the oxidative stress environment of cancer cells, which may contribute to its chemoprevention and cytotoxicity in SCC. 5,6,12,16 As early as 1999, Badary et al…”

“…Beginning in the 1990's, the anticancer effects of thymoquinone (TQ), the active constituent in the plant Nigella sativa ( N. sativa ), have been studied in squamous cell carcinoma (SCC) 2–18 . TQ has been found to have anticancer effects in many types of SCC including cervical SCC, gastric SCC, and head and neck SCC (HNSCC) 2,9,12,14 .…”

“…TQ is particularly light sensitive and has poor solubility in aqueous solutions ranging 549–669 μg/mL 26 . Ongoing research to enhance efficacy of TQ administration aims to improve TQ's bioavailability via delivery through various nanoformulations, like TQ loaded on gold nanoparticles (TQ‐GNps) 4–6,27–31 . The lethal dose (LD 50 ) of TQ depends on the route and vehicle of administration, as well as the type of species in which it is studied.…”