A Solanum incanum extract (SR-T100) regresses vulvar condyloma acuminatum and induces distinct autophagic and apoptotic responses in different types of HPV-infected cells
نویسندگان
چکیده
Background: The Solanum species have been used for the treatment of warts, tumor and cancer in folk medicine. The S. incanum extract is an important traditional Chinese medicine in Taiwan since 1973. The purpose of the present study was to evaluate the efficacy and safety of Solanum incanum (synonym: Solanum undatum) extract (SR-T100), a water-soluble product primarily composed of alkaloid solamargine, for the treatment of human condyloma and to study the possible underlying anti-condyloma mechanisms. Methods: We conducted a pilot study to test the effectiveness and side effects of SR-T100 gel (2.3% solamargine in Solanum incanum plant extract) for the treatment of external genital warts. We produced different types of human papillomavirus (HPV) E6/E7-infected cells by lentiviral technology and studied the differences in apoptosis and autophagy between these cells under the treatment of SR-T100. Results: Nineteen (73%) of 26 patients using the SR-T100 gel exhibited a response, and 16 (61.5%) patients achieved total clearance. Only one patient showed severe (grade 3-4) skin-related side effects. SR-T100 induced mitochondriadependent apoptosis in HPV-infected cells. Cells expressing the high-risk HPV E6/E7 type were resistant to SR-T100induced apoptosis. SR-T100 induced a greater autophagic response in HPV 16, 18-E6/E7 cells than in HPV 6b, 11-E6/E7 cells. Autophagy inhibition enhanced SR-T100-induced apoptosis in HPV 16, 18-E6/E7 cells, whereas apoptosis inhibition enhanced SR-T100-induced autophagy in HPV 6b, 11-E6/E7 cells. Conclusions: SR-T100 is effective for the treatment of human vulva condyloma, with few side effects. Compared with those with high-risk HPVs, cells with low-risk HPVs were more sensitive to SR-T100 treatment. Autophagy played a protective role in SR-T100-induced apoptosis in HPV-infected cells. Trial registration: NCT01676792; Registered: August 29, 2012 (retrospectively registered).
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