title: Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway.
abstract: BACKGROUND
  The Solanum species herbs have been used to treat cancer for centuries; however, the underlying mechanisms and effectiveness in vivo remain unclear.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Dermatology, National Cheng Kung University College of Medicine and Hospital, 138 Sheng-Li Road, Tainan, Taiwan.
authors: Chin-Han
authors: CH
authors: Wu
authors: Chia-Hua
authors: CH
authors: Liang
authors: Li-Yen
authors: LY
authors: Shiu
authors: Li-Ching
authors: LC
authors: Chang
authors: Tsai-Shiuan
authors: TS
authors: Lin
authors: Cheng-Che Eric
authors: CC
authors: Lan
authors: Jui-Chen
authors: JC
authors: Tsai
authors: Tak-Wah
authors: TW
authors: Wong
authors: Kai-Jhe
authors: KJ
authors: Wei
authors: Tzu-Kai
authors: TK
authors: Lin
authors: Nan-Shan
authors: NS
authors: Chang
authors: Hamm-Ming
authors: HM
authors: Sheu