In VivoAntineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis Model

Abstract

The antineoplastic properties of the NSAID sulindac have long been studied. The purpose of this study was to explore sulindac's in vivo effects on oral squamous cell carcinoma (SCC) oncogenesis using the hamster cheek pouch oral carcinogenesis model (HOCM). Thirty Syrian golden hamsters were divided into three experimental and two control groups (n ¼ 6 each). The animals' right buccal pouches were treated with carcinogen for 9 weeks in one experimental and one control group and for 14 weeks in all other three groups. The animals of two experimental groups received sulindac from the 1st week and those of the third experimental group from the 10th week. After the end of carcinogenesis, treated buccal pouches were removed and examined. In animals treated with carcinogen for 14 weeks, development of oral SCC and tumor volume were significantly lower in animals that received sulindac from the first week of the experiment. Oral SCC developing in animals that received sulindac were more frequently well differentiated compared with the control group. In animals treated with carcinogen for 9 weeks, the animals that received sulindac developed lower grade of epithelial dysplasia. Proliferation index Ki-67 and positivity for the antiapoptotic molecule survivin were lower in the animals that received sulindac. Treatment with sulindac appears to delays the progression of oral premalignant lesions to oral SCC in the HOCM, also resulting in smaller and better differentiated tumors. These in vivo antineoplastic effects may be related to sulindac's ability to decrease cell proliferation and to prevent survivin expression.

Expression of AKR1B10 as an independent marker for poor prognosis in human oral squamous cell carcinoma

“…Notably, sulindac, a nonsteroidal anti‐inflammatory drug, inhibits pancreatic carcinogenesis through the inhibition of K‐ras protein prenylation by targeting AKR1B10 . Moreover, sulindac has been shown to inhibit cell proliferation and tumor growth in an oral carcinogenesis model . A recent study showed that AKR1B10 overexpression conferred resistance to cisplatin in A549 cells .…”

“…34 Moreover, sulindac has been shown to inhibit cell proliferation and tumor growth in an oral carcinogenesis model. 35 A recent study showed that AKR1B10 overexpression conferred resistance to cisplatin in A549 cells. 36 Cisplatin resistance reduces survival in patients with advanced stage head and neck SCC.…”

Efficacy of Hydroxytyrosol as Chemopreventive Agent on Induced Hamster Buccal Pouch Carcinogenesis

“…Moreover, the results of H&E stain and IHC staining utilizing Bcl-2 and Bak antibodies revealed variable observations. The HBP oral carcinogenesis model in the current study was used because is the best known animal system that closely correlates with sequential common events involved in the development of human oral premalignant and malignant lesion (16) .…”

Synthesis of (R)-Modafinil via Organocatalyzed and Non-Heme Iron-Catalyzed Sulfoxidation Using H2O2 as an Environmentally Benign Oxidant

“…There are several examples that playing an important role in medicinal and pharmaceutical chemistry [2], including Esomeprazole [7,8], which acts as proton-pump inhibitor; the selective NK 2 antagonist ZD7944 [9]; and the anti-cancer agent Sulindac ® (Figure 1) [10].…”

“…There are several examples that playing an important role in medicinal and pharmaceutical chemistry [2], including Esomeprazole [7,8], which acts as proton-pump inhibitor; the selective NK2 antagonist ZD7944 [9]; and the anti-cancer agent Sulindac ® (Figure 1) [10]. Modafinil (also known as Provigil ® [11], Figure 2), another important sulfoxide, is administered as a drug against narcolepsy [12] with significant advantages compared to dexamphetamine [13] and several other stimulants [14] because of a lower abuse potential [15,16].…”