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

Chin Han Wu; Chia Hua Liang; Li Yen Shiu; Li Ching Chang; Tsai Shiuan Lin; Cheng Che Eric Lan; Jui Chen Tsai; Tak Wah Wong; Kai Jhe Wei; Tzu Kai Lin; Nan Shan Chang; Hamm Ming Sheu

doi:10.1016/j.jdermsci.2011.04.003

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

Chin Han Wu, Chia Hua Liang, Li Yen Shiu, Li Ching Chang, Tsai Shiuan Lin, Cheng Che Eric Lan, Jui Chen Tsai, Tak Wah Wong, Kai Jhe Wei, Tzu Kai Lin, Nan Shan Chang, Hamm Ming Sheu

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Abstract

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.

Original language	English
Pages (from-to)	83-92
Number of pages	10
Journal	Journal of Dermatological Science
Volume	63
Issue number	2
DOIs	https://doi.org/10.1016/j.jdermsci.2011.04.003
Publication status	Published - 2011 Aug

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Biology
Dermatology

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10.1016/j.jdermsci.2011.04.003

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Wu, C. H., Liang, C. H., Shiu, L. Y., Chang, L. C., Lin, T. S., Lan, C. C. E., Tsai, J. C., Wong, T. W., Wei, K. J., Lin, T. K., Chang, N. S., & Sheu, H. M. (2011). Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway. Journal of Dermatological Science, 63(2), 83-92. https://doi.org/10.1016/j.jdermsci.2011.04.003

@article{125161a5ed70442883a99d52ff9bd4ce,

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. 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.",

author = "Wu, {Chin Han} and Liang, {Chia Hua} and Shiu, {Li Yen} and Chang, {Li Ching} and Lin, {Tsai Shiuan} and Lan, {Cheng Che Eric} and Tsai, {Jui Chen} and Wong, {Tak Wah} and Wei, {Kai Jhe} and Lin, {Tzu Kai} and Chang, {Nan Shan} and Sheu, {Hamm Ming}",

note = "Funding Information: We thank Shih-Hao Lo and Shu-Miao Chen for technical assistance. SR-T100 was kindly gifted by Professor Kou-Wha Kuo, Research Center of Herbal Medicines, G&E Herbal Biotechnology, National Tainan Science Park, Tainan 744, Taiwan. The research was supported in part by the National Science Council, Executive Yuan, Taipei, Taiwan, grants NSC96-2314-B-006-044-MY2, NSC96-2314-B-006-016-MY2, NSC98C34, and NSC97-2320-B-041-002-MY3, National Tainan Science Park of Taiwan (95-1002-B082-002), and Ministry of Economic Affairs of Taiwan (93-EC-17-A-20-I1-0051 and 97-EC-17-A-20-I1-0003). ",

year = "2011",

month = aug,

doi = "10.1016/j.jdermsci.2011.04.003",

language = "English",

volume = "63",

pages = "83--92",

journal = "Journal of Dermatological Science",

issn = "0923-1811",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

Wu, CH, Liang, CH, Shiu, LY, Chang, LC, Lin, TS, Lan, CCE, Tsai, JC, Wong, TW, Wei, KJ, Lin, TK, Chang, NS & Sheu, HM 2011, 'Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway', Journal of Dermatological Science, vol. 63, no. 2, pp. 83-92. https://doi.org/10.1016/j.jdermsci.2011.04.003

TY - JOUR

T1 - Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway

AU - Wu, Chin Han

AU - Liang, Chia Hua

AU - Shiu, Li Yen

AU - Chang, Li Ching

AU - Lin, Tsai Shiuan

AU - Lan, Cheng Che Eric

AU - Tsai, Jui Chen

AU - Wong, Tak Wah

AU - Wei, Kai Jhe

AU - Lin, Tzu Kai

AU - Chang, Nan Shan

AU - Sheu, Hamm Ming

N1 - Funding Information: We thank Shih-Hao Lo and Shu-Miao Chen for technical assistance. SR-T100 was kindly gifted by Professor Kou-Wha Kuo, Research Center of Herbal Medicines, G&E Herbal Biotechnology, National Tainan Science Park, Tainan 744, Taiwan. The research was supported in part by the National Science Council, Executive Yuan, Taipei, Taiwan, grants NSC96-2314-B-006-044-MY2, NSC96-2314-B-006-016-MY2, NSC98C34, and NSC97-2320-B-041-002-MY3, National Tainan Science Park of Taiwan (95-1002-B082-002), and Ministry of Economic Affairs of Taiwan (93-EC-17-A-20-I1-0051 and 97-EC-17-A-20-I1-0003).

PY - 2011/8

Y1 - 2011/8

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=79959844911&partnerID=8YFLogxK

U2 - 10.1016/j.jdermsci.2011.04.003

DO - 10.1016/j.jdermsci.2011.04.003

M3 - Article

C2 - 21612892

AN - SCOPUS:79959844911

SN - 0923-1811

VL - 63

SP - 83

EP - 92

JO - Journal of Dermatological Science

JF - Journal of Dermatological Science

IS - 2

ER -

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

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