Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/26682
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    標題: Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway
    作者: Wu, Chin-Han
    Liang, Chia-Hua
    Shiu, Li-Yen
    Chang, Li-Ching
    Lin, Tsai-Shiuan
    Lan, Cheng-Che Eric
    Tsai, Jui-Chen
    Wong, Tak-Wah
    Wei, Kai-Jhe
    Lin, Tzu-Kai
    Chang, Nan-Shan
    Sheu, Hamm-Ming
    貢獻者: 化粧品應用與管理系
    關鍵字: Apoptosis
    Squamous cell carcinoma
    Actinic keratosis
    Solanum incanum
    Solamargine
    日期: 2011-08
    上傳時間: 2013-06-03 15:53:05 (UTC+8)
    出版者: Elsevier
    摘要: Background
    The Solanum species herbs have been used to treat cancer for centuries; however, the underlying mechanisms and effectiveness in vivo remain unclear.

    Objectives
    SR-T100, extracted from the Solanum incanum, contains solamargine alkaloid as the main active ingredient. Here, we investigated the apoptosis-inducing effects of SR-T100 for targeting squamous cell carcinoma (SCC) in vitro and in vivo.

    Methods
    We elucidated the mechanism by which SR-T100 induces apoptosis of human SCCs (A431, SCC4, SCC9, and SCC25) cells. The efficacy and safety issues were addressed regarding topical treatment of SR-T100 on UVB-induced cutaneous SCC of hairless mice and actinic keratoses (AKs) of human.

    Results
    SR-T100 induces apoptosis in human SCCs cell lines by up-regulating the expressions of tumor necrosis factor receptors (TNFRs) and Fas, and downstream adaptors FADD/TRADD of the TNF-α and Fas ligand signaling cascades. SR-T100 also triggered the mitochondrial apoptotic pathway, as up-regulated cytochrome c and Bax, down-regulated Bcl-XL. Animal experiments showed that all papillomas (35/35) and 27 of 30 UVB-induced microinvasive SCCs in hairless mice disappeared within 10 weeks after once-daily application of topical SR-T100. Furthermore, 13 patients, who suffered with 14 AKs, were treated with once-daily topical SR-T100 gel and 10 AKs cured after 16 weeks, showing negligible discomforts.

    Conclusion
    Our studies indicate that SR-T100 induces apoptosis of SCC cells via death receptors and the mitochondrial death pathway. The high efficacy of SR-T100 in our preclinical trial suggests that SR-T100 is a highly promising herb for AKs and related disorders.

    Abbreviations
    5-FU, 5-fluorouracil; AKs, actinic keratosis; FADD, Fas-associated death domain; FasL, Fas ligand; FDA, Food and Drug Administration; MISCC, microinvasive squamous cell carcinomas; NMSC, non-melanoma skin cancers; PCNA, proliferating cell nuclear antigen; PI, propidium iodide; RT-PCR, reverse transcription-polymerase chain reaction; SCC, squamous cell carcinoma; TNFRs, tumor necrosis factor receptors; TRADD, TNFR-1-associated death domain; TUNEL, terminal nucleotidyl transferase-mediated nick and labeling; UV, ultraviolet
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