Abstract 1595: Comparing a topical-based curcumin to dietary curcumin in a skin cancer model

Abstract

Abstract Objective: Curcumin has been under investigation for its anti-carcinogenic role in a variety of human cancers. However curcumin clinical trials in skin carcinoma have not been reported. Skin squamous cell carcinoma (SCC) is an aggressive tumor associated with higher rates of metastasis and recurrences, especially in the lymphatic rich head and neck region. Low oral bioavailability has been a limitation in clinical trials with curcumin. We investigated curcumin's chemopreventive properties to prevent or delay skin SCC growth when administered topically versus orally. We also wanted to determine biomarkers of response for future chemopreventive trials given the aggressive nature of the disease, problems of condemned skin, recurrences and metastases, and rising health care costs. This is the first study comparing topical to oral curcumin in a mouse model. Methods: 6-8 week-old SCID mice were pretreated with 15 mg corn oil (control), 15 mg curcumin by oral gavage, curcumin topical paste, or combined oral gavage and topical paste (n=10/group) daily for 3 days prior to the subcutaneous injection of SRB-12 P9 cells (aggressive skin SCC). Mice were treated and tumors measured daily by digital calipers, and sacrificed on day 29. Tumors with overlying skin and blood were collected. Results and Discussion: Tumor volumes from all curcumin treated groups were significantly smaller compared to the control group (p<0.001). Ex vivo tumor volumes from all curcumin treated groups were significantly smaller than the control (p= 0.004). There was no difference between the curcumin gavage and topical tumor volumes (p = 0.19). Western blot analysis of xenograft tumors showed significant inhibition of pS6, a well known downstream target of MTOR inhibitors and MEK/ERK pathway in gavage and combined treated groups but did not show the same inhibition of pMTOR or p4EBP1. pERK and pSTAT3 was significantly inhibited in all curcumin treated groups, and inhibition was more pronounced in the combined curcumin group. There was no difference of pERK and pSTAT3 expression between the curcumin gavage and topical group. IHC showed strong positive pERK staining throughout tumors in the control group, and weaker, focal staining in the curcumin-treated tumors. There was no difference in pERK staining between the curcumin gavage and topical group. ELISA on pooled serum obtained from mice showed the inflammatory marker IL-6 was significantly inhibited in the topical group, but not in the groups receiving systemic curcumin. Conclusion: Curcumin inhibited tumor growth in all treated groups and topical curcumin was equally effective as oral curcumin in inhibiting tumor growth. Combined with its anti-carcinogenic effects, curcumin's local anti-inflammatory properties can contribute to its role as a chemopreventive agent. Targets of the ERK pathway appear to be promising biomarkers of response for future curcumin chemopreventive trials in skin SCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1595. doi:1538-7445.AM2012-1595