ABSTRACT
ABSTRACT Leishmania infantum is an etiologic agent of visceral leishmaniasis. This disease is a neglected disease that can be fatal if not treated and additionally, the few therapeutic option present several drawbacks, including difficult route of administration and toxicity, which turn the search for new therapeutic alternatives necessary. Herein, we evaluated the leishmanicidal in vitro activity of the solanum extract from Solanum lycocarpum A. St.-Hil., Solanaceae, and the isolated alkaloids solasodine, solamargine and solasonine against promastigotes and intracellular amastigotes of L. infantum. Solasodine (IC50-pro = 4.7 µg/ml; IC50-ama = 10.8 µg/ml) and solamargine (IC50-pro = 8.1 µg/ml; IC50-ama = 3.0 µg/ml) exhibited interesting leishmanicidal ativity. Solasonine was approximately four-times (Selective Index 3.7) more selective to the parasite than to the host cells. This data suggest that solasonine might be considered as a potential drug candidate for leishmaniasis treatment.
ABSTRACT
Objective: To study the in vitro antiproliferative effect and probable mechanism of solasonine on human breast cancer Bcap-37 cells, meanwhile, make comparison with solamargine. Methods: The cytotoxicity was evaluated by MTT assay. The cell damage and type of cell death were examined through Hoechst33342/PI and Annexin V/PI staining, respectively. Mitochondrial membrane potential was detected by JC-1 staining. The expression of Bcl-2, Bcl-xL, Bax, and cytochrome c was determined by immunoblot method, and the activation of caspase-3 was analyzed by immunocytochemistry method. Results: Solasonine showed the different extents of cytotoxicity on eight human tumor cell lines as well as four human normal cell lines, and the IC50 values of solasonine ranged from 12.73 to 37.15 μmol/L. Cell apoptosis and mitochondria depolarization were observed in Bcap-37 cells after treatment with solasonine for 24 h, respectively. In immunoblot and immunocytochemistry analysis, solasonine obviously induced the up-regulation of Bax and down-regulation of Bcl-2 and Bcl-xL, caused the release of cytochrome c from mitochondria into cytosol, and increased the expression of both pro- and cleaved caspase-3. Solamargine exhibited stronger antipoliferative activity than solasonine, but the similar mechanism in Bcap-37 cells in this study. Conclusion: Solasonine possesses the antiproliferative effect on tumor cells. Regulation of the levels of Bcl-2, Bcl-xL, Bax, and activation of mitochondria cytochrome c-dependent apoptosis pathway might be one of its main antitumor mechanisms against breast cancer cells. In view of the cytotoxic effect of solasonine and solamargine also shown on normal cells, the safety needs concern when the antitumor activity is studied.
ABSTRACT
The majority of penile cancers develop from squamous cells within the skin resulting in a non-melanoma form of skin cancer, squamous cell carcinoma. Squamous cell carcinomas can develop anywhere on the penis, most appear on the foreskin in men who have not been circumcised or on the glans. Various types of squamous cell carcinomas ranging from Bowen’s disease, erythroplasia of Queyrat and Buschke- Lowenstein tumour have been identified on the penis. When detected early, these types of cancer can be successfully treated. However, the current treatment procedures have the potential for disfigurement and dysfunction of male genitalia, with associated psychological distress. A relatively new class of antineoplastic agents, consisting of the solasodine rhamnosides, solamargine and solasonine, are very effective and safe for the treatment of a variety of skin cancers and show promise for the treatment of internal cancers. Here, three cases of distinct squamous cell carcinomas on the penis, Bowen’s disease, erythroplasia of Queyrat and Buschke-Lowenstein tumour are reviewed which were successfully treated with a standard mixture of solasodine rhamnosides.