title: Topical phospho-sulindac (OXT-328) is effective in the treatment of non-melanoma skin cancer.
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.
authors: Division of Cancer Prevention, Department of Medicine, Stony Brook University, Stony Brook, NY, USA.
authors: Ka Wing
authors: KW
authors: Cheng
authors: George
authors: G
authors: Mattheolabakis
authors: Chi C
authors: CC
authors: Wong
authors: Nengtai
authors: N
authors: Ouyang
authors: Liqun
authors: L
authors: Huang
authors: Panayiotis P
authors: PP
authors: Constantinides
authors: Basil
authors: B
authors: Rigas
mesh_terms: D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051379:Mice; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013467:Sulindac / Q000008:administration & dosage / Q000031:analogs & derivatives*; D023041:Xenograft Model Antitumor Assays
chemical_list: C553002:OXT-328; D009943:Organophosphorus Compounds; D013467:Sulindac