tetraphenylporphine and Skin-Neoplasms

Structure-activity relationships of ursane-type pentacyclic triterpenes obtained from natural sources and by chemical derivatization are reviewed. Ursolic acid, corosolic acid, and a new ursane-type pentacyclic triterpene, 7,24-dihydroxyursolic acid, were isolated from the methanolic extract of the leaves of the Bangladeshi medicinal plant, Saurauja roxburghii. Derivatization of ursolic acid by oxidation with dioxoruthenium (VI) tetraphenylporphyrins was investigated. Oxidation selectivity on the terpene structure was modulated by the auxiliaries introduced on the tetraphenylporphyrin. The natural triterpenes and oxidized derivatives were tested for cytotoxicity against the C6 rat glioma and A431 human skin carcinoma cell lines. Although they have the same ursane-type pentacyclic triterpene cores, the position and numbers of hydroxyls on the terpene structures significantly affected the activity and the selectivity towards the tested cell lines.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Humans; Oxidation-Reduction; Plant Extracts; Plant Leaves; Porphyrins; Rats; Skin Neoplasms; Structure-Activity Relationship; Triterpenes; Ursolic Acid

Photodynamic therapy (PDT) is a non-surgical method for treating non-melanoma skin cancer and precancerous lesions which involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in the destruction of the latter. The present study evaluates the effect of PDT on primary normal and basal cell carcinoma cultures in vitro.. Primary human keratinocytes and carcinoma cell cultures were exposed to various concentrations of 5,10,15,20-tetra-(para-methoxyphenyl) porphyrin (TMP) and its zinc compound (Zn-TMP) for 24 hours, with or without chitosan, and then irradiated using a PDT lamp (630 nm, 6 J/cm(2)). The effects of PDT were assessed using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay and an immunocytochemical method with Annexin V-FITC for detecting apoptosis.. Both tested substances, TMP and Zn-TMP, had a phototoxic effect on primary human carcinoma cell cultures in concentrations of 1-100 μg/ml, which positively correlated with the concentration of the photosensitizer. There was no phototoxic effect on primary keratinocytes, probably because of the preferential accumulation of photosensitizing substances in tumoral cells. Administration of chitosan in association with photosensitizing substances increased cell viability compared with photosensitizers alone, exerting a cytoprotective effect.. The study demonstrates that the photodynamic activity of TMP and its metalloporphyrin derivative is limited to primary human carcinoma cells and suggests that these porphyrins could be efficiently used in PDT in vivo.

Topics: Apoptosis; Biocompatible Materials; Carcinoma, Basal Cell; Cell Survival; Chitosan; Humans; In Vitro Techniques; Keratinocytes; Photochemotherapy; Photosensitizing Agents; Porphyrins; Skin Neoplasms; Tumor Cells, Cultured; Zinc Compounds