Topical phospho-sulindac (OXT-328) is effective in the treatment of non-melanoma skin cancer

Cheng,Ka  Wing; Mattheolabakis,George; Wong,Chi  C.; Ouyang,Nengtai; Huang,Liqun; Constantinides,Panayiotis  P.; Rigas,Basil

doi:10.3892/ijo.2012.1577

Topical phospho-sulindac (OXT-328) is effective in the treatment of non-melanoma skin cancer

Authors:
- Ka Wing Cheng
- George Mattheolabakis
- Chi C. Wong
- Nengtai Ouyang
- Liqun Huang
- Panayiotis P. Constantinides
- Basil Rigas
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Affiliations: Division of Cancer Prevention, Department of Medicine, Stony Brook University, Stony Brook, NY, USA, Medicon Pharmaceuticals Inc., Stony Brook, NY, USA
Published online on: July 27, 2012 https://doi.org/10.3892/ijo.2012.1577
Pages: 1199-1203
Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Phospho-sulindac (P-S, OXT-328), a novel sulindac derivative, has shown superior anticancer efficacy and safety compared to sulindac. In this study, we investigated the efficacy of topical P-S hydrogel in the treatment of non-melanoma skin cancer in preclinical models. P-S is a potent inhibitor of A431 epidermoid carcinoma in vitro and achieves this effect by inhibiting cell proliferation and inducing apoptosis. The anticancer efficacy of topical and oral P-S was further evaluated in mice bearing A431 intradermal xenografts. Compared to the controls, topical P-S hydrogel inhibited the A431 xenografts by 70.5% (p<0.01), while oral P-S inhibited it by 43.4% (p<0.05), being significantly less effective than topical P-S (p=0.017). Topical P-S hydrogel generated significant levels (>500 nmol/g tumor tissue) of intact P-S in the tumors, accounting for 92.5% of the total metabolites in the A431 xenografts. This local delivery of high levels of intact P-S to the A431 xenografts is an important contributor to the potent activity of topical P-S and no local or systemic side effects were noted in the treatment group. Thus, topical P-S is a promising treatment modality against non-melanoma skin cancer and merits further evaluation.

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