XRCC1 immunohistochemical expression in DMBA – induced oral squamous cell carcinoma treated with different thymoquinone preparations

Abstract

Introduction: The X-ray repair cross-complementing 1 (XRCC1) enzyme plays an important role in the DNA repair pathway. XRCC1 polymorphism increased the risk of human oral squamous cell carcinoma. Loading of thymoquinone on gold nanoparticles as a drug carrier, had revealed a superior anti-cancer effect as a chemotherapeutic agent in DMBA-induced OSCC. Aim of the work: This study aimed to evaluate the expression of DNA repair enzyme X-ray repair cross-complementing 1 (XRCC1) following treatment of induced oral cancer in hamster buccal pouch with thymoquinone (TQ) only and loaded on gold nanoparticles (AuNps). Materials and methods: Sixty male Syrian golden hamsters were divided into 4 groups: Group A: (negative control). The left pouches of the rest of animals were painted with the carcinogen DMBA (3times / week/ 12 weeks), then: Group B: (positive control), Group C: painted and injected intraperitoneally (i.p) with TQ only (3 times/week for 6 and 12 weeks). Group D: painted with TQ loaded on AuNps (3 times/week for 6 and 12 weeks). After euthanization, all pouches were surgically excised, fixed and processed for H&E and XRCC1 immunohistochemical stains. Results: Groups B, C1, C2, and D1 showed well-differentiated squamous cell carcinoma with low intensity of immune staining. Groups D2 showed remarkable regression of tumors both clinically and histologically with high intensity of IHC staining. Conclusion: Loading of TQ at low concentration (0.001 mg/kg) on AuNps /12 weeks was a promising chemotherapeutic combination, through enhancing XRCC1 expression to regress the carcinogenesis process. This effect could be due to the anti-oxidant, free-radicle scavenging effect and enhancing apoptosis by TQ.

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.…”