Chinese herbal medicine Huang Qin (Scutellaria baicalensis) has a variety of anti-inflammatory and anti-cancer activities. The central hypothesis of this proposal is that Scutellaria baicalensis extracts (SBE) inhibit ultraviolet (UV) B-induced pyrimidine dimers and oxidative DNA damage, and modulate UVB-activated signal transduction cascades and inflammatory responses, thereby suppressing the initiation and promotion of photocarcinogenesis. The initial aim of the project is to determine if pre- or post-application of SBE prevents UVB-induced skin carcinogenesis. The initial aim of the project is to determine if pre- or post-application of SBE prevents UVB-induced skin carcinogenesis. SBE will be topically applied to hairless mice during exposure to UVB. The protective effect will be evaluated by analyzing the latency period, tumor incidence and multiplicity.
The second aim i s to evaluated the effects of SBE on the initiation, promotion, and progression of photocarcinogenesis. A combined UVB-carcinogen model will be used to dissect the anti-initiational or anti-promotional effects of SBE on UBV- induced skin carcinogenesis. SBE will be topically applied to mouse skin before an initiating dose of UVB, followed by TPA promotion, or applied before UCB radiation in DMBA-initiated mice. The therapeutic effect of SBE will be tested on the existing cutaneous tumors by recording the tumor regression rate and malignant conversion rate.
The third aim i s to determine if SBE modifies UVB-induced intermediate endpoints relevant to initiation and promotion, e.g. DNA photoproducts, oxidative DNA damage, inflammatory responses, protooncogene expression and activation of AP-1 factor in vivo and in vitro. Lastly, we will further evaluate the efficacy of SBE in protection of UVB-induced erythema and discomfort in human skin. The molecular markers of DNA damage (pyrimidine dimers and 8-OHdG), apoptosis (p53 protein expression), and cell proliferation (PCNA) will be determined in the human skin biopsies as well as in 3-dimensional reconstituted human skin chronically exposed to UVB. Successful completion of the proposed studies will not only contribute to innovative use of herbal extracts as preventive and/or therapeutic agents against human skin cancer, but also promote the research on the anti-cancer action of BE in other human malignancies.
