Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway

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• 作者：Chin-Han Wu^a ; ^b ; ¹ ; Chia-Hua Liang^c ; ¹ ; Li-Yen Shiu^d ; Li-Ching Chang^e ; Tsai-Shiuan Lin^a ; ^b ; Cheng-Che Eric Lan^f ; Jui-Chen Tsai^g ; Tak-Wah Wong^a ; ^h ; ⁱ ; Kai-Jhe Wei^a ; Tzu-Kai Lin^a ; Nan-Shan Chang^j ; Hamm-Ming Sheu^a ; ^{hmsheu@mail.ncku.edu.tw"" rel=""nofollow}
• 关键词：Apoptosis ; Squamous cell carcinoma ; Actinic keratosis ; Solanum incanum ; Solamargine
• 刊名：Journal of Dermatological Science
• 出版年：2011
• 出版时间：August 2011
• 年：2011
• 卷：63
• 期：2
• 页码：83-92
• 全文大小：2190 K

文摘

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-X_L. 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.