Drug therapy: Solamargine and other solasodine rhamnosyl glycosides as anticancer agents

Bill E. Cham

Australasian Institute of Medical Research, Brisbane, Australia.

DOI: 10.4236/mc.2013.22005                

Abstract

In the last century, the discovery of cytotoxic agents was revolutionary for anticancer therapy. These therapies have resulted in better understanding of cancer in general. However, the development of agents that combine efficacy, safety and convenience remains a great challenge. The narrow, if not adverse, therapeutic index of most drugs, the damage not only to cancer cells, but also to normal and healthy tissue and the occurrence of resistance have limited anticancer efficacy. This review presents the development of promising novel cytotoxic solasodine rhamnosyl glycoside drugs that offer not only gains in specificity and efficacy, but also in safety, tolerability, non-resistance and convenience in the treatment of patients with cancer.

Keywords

Cancer; Skin Cancer; Solamargine; Solasonine; BEC; Solasodine Rhamnosyl Glycosides; Curaderm^BEC5; Apoptosis; Antineoplastic; Targeted Therapy

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Cham, B.E. and Wilson, L. (1987) HPLC of glycoalkaloids from Solanum sodomaeum L. Planta Medica, 53, 59-61. doi:10.1055/s-2006-962621
[2]	Cham, B.E., Gilliver, M. and Wilson, L. (1987) Antitumour effects of glycoalkaloids isolated from Solanum sodomaeum L. Planta Medica, 53, 34-36. doi:10.1055/s-2006-962612
[3]	Daunter, B. and Cham, B.E. (1990) Solasodine glycosides. In vitro preferential cytotoxicity for human cancer cells. Cancer Letters, 55, 209-220. doi:10.1016/0304-3835(90)90121-D
[4]	Cham, B.E. and Daunter, B. (1990) Solasodine glycosides. Selective cytotoxicity for cancer cells and inhibition of cytotoxicity by rhamnose in mice with sarcoma 180. Cancer Letters, 55, 221-225. doi:10.1016/0304-3835(90)90122-E
[5]	Cham, B.E. (1993) Efficacy and mode of action of solasodine gly-cosides (BEC) on cancer cells. Proceedings of 4th Oceania Symposium, Bioconcepts Publishing, 41-51.
[6]	Nakamura, T., Komori, C., Lee, Y., Hashinoto, F., Yahara, S., Nohara T. and Ejina, A. (1996) Cytotoxic activities of Solanum steroidal glycosides. Biological Bi-opharmaceutical Bulletin, 19, 564-566. doi:10.1248/bpb.19.564
[7]	Hsu, S.H., Tsai, T.R., Lin, C.N., Yen, M.H. amd Kuo, K.W. (1996) Solamargine pu-rified from Solanum incanum Chinese herb triggers gene expression of human TNFR1 which may lead to apoptosis. Biochemical and Biophysical Research Communication, 229, 1-5. doi:10.1006/bbrc.1996.1748
[8]	Chang, L.C., Tsai, T.R., Wang, J.J., Lin, C.N. and Kuo, K.W. (1998) The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis. Biochemical and Biophysical Research Communication, 242, 21-25. doi:10.1006/bbrc.1997.7903
[9]	Kuo, K.W. and Lin, C.N. (1999) Pharmacological composition for treating cancer cells. US Patent No. 6214803.
[10]	Kuo, K.W., Hsu, S.H., Li, Y.P., Lin, W.L., Liu, L.F., Chang, L.C., Lin, C.C., Lin, C.N. and Sheu, H.M. (2000) Anticancer activity evaluation of the Solanum glycoalkaloid solamargine. Triggering apoptosis in human hepatoma cells. Bio-chemical Pharmacology, 60, 1865-1873. doi:10.1016/S0006-2952(00)00506-2
[11]	Esteves-Souza, A., Silva T.M. and Alves, C.C.F. (2002) Cytotoxic ac-tivities against Ehrlich carcinoma and human K562 leu-kemia of alkaloids and flavonoid from two Solanum species. Journal of Brazil Chemical Society, 13, 838-842. doi:10.1590/S0103-50532002000600017
[12]	Solbec Pty Ltd. http://www.solbec.com.au
[13]	Lee, K.R., Kozukue, N.J., Han, S.J., Park, H., Chang, E.Y., Back, E.J., Chang J.S. and Friedman, M. (2004) Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells. Journal of Agricultural Food Chemistry, 52, 2832-2839. doi:10.1021/jf030526d
[14]	Liu, L.F., Liang, C.H., Shiu, L.Y., Lin, W.L., Lin, C.C. and Kuo, K.W. (2004) Action of solamargine on human lung cancer cells-enhancement of the susceptibility of cancer cells to TNFs. FEBS Letters, 577, 67-74. doi:10.1016/j.febslet.2004.09.064
[15]	Lipscombe, R.J., Carter, S.J. and Ruane, M. (2005) Rhamnose binding protein. US Patent No. 6930171.
[16]	He, D.J. (2006) Structure and anticancer activity of glycoalkaloids. Master’s Thesis.
[17]	Ono, M., Nishimura, K.K., Suzuki, T., Fukushima, K., Igoshi, H., Yoshimitsu, H., Ikeda, T. and Nohara, T. (2006) Steroidal glycosides from the un-derground parts of Solanum sodomaeum. Chemical Pharmacy Bulletin, 54, 230-233. doi:10.1248/cpb.54.230
[18]	Shiu, L.Y., Chang, L.C., Liang, C.H., Huang, Y.S., Sheu, H.M. and Kuo, K. W. (2007) Solamargine induces apoptosis and sensitizes breast cancer cells to cisplatin. Food Chemical Toxicology, 45, 2155-2164. doi:10.1016/j.fct.2007.05.009
[19]	Liang, C.H., Shiu, L.Y., Chang, L.C., Sheu, H.M., Kuo, K.W. (2007) Sola-margine upregulation of Fas, down-regulation of HER2, and enhancement of cytotoxicity using epirubicin in NSCLC cells. Molecular Nutrition Research, 51, 999-1005. doi:10.1002/mnfr.200700044
[20]	Shiu, L.Y., Liang, C.H., Chang, L.C., Sheu, H.M., Tsai, E.M. and Kuo, K.W. (2009) Solamargine induces apoptosis and enhances susceptibility to trastazumab and epirubicin in breast cancer cells with low or high expression levels of HER2/neu. Bioscience Reports, 29, 35-45. doi:10.1042/BSR20080028
[21]	Sun, L., Zhao, Y., Li, X., Yuan, H., Cheng, A. and Lou, H. (2010) A lysosom-al-mitochondrial death pathway is induced by solamar-gine in human K562 leukemia cells. Toxicology in Vitro, 24, 1504-1511. doi:10.1016/j.tiv.2010.07.013
[22]	Sun, L., Zhao, Y., Yuan, H., Li, X., Cheng A. and Lou, H. (2010) Solamar-gine, a steroidal alkaloid glycoside, induces oncosis in human K562 leukemia and squamous cell carcinoma KB cells. Cancer Chemotherapy Pharmacology, 65, 1125-1130.
[23]	Li, X., Zhao, Y., Wu, W.K.K., Liu, S., Cui, M. and Lou, H. (2011) Solamargine induces apopto-sis associated with p53 transcription-dependent and tran-scription-independent pathways in human osteosarcoma U20S cells. Life Science, 88, 314-321. doi:10.1016/j.lfs.2010.12.006
[24]	Wang, Y., Gao, J., Gu, G., Li, G., Cui, C., Sun, B. and Lou, H. (2011) In situ RBL receptor visualization and its mediated anticancer activity for solasodine rhamnosides. Chemistry Biochemistry, 12, 2418-2420. doi:10.1002/cbic.201100551
[25]	Cham, B.E. and Chase, T.R. (2012) Solasodine rhamnosyl glycosides cause apoptosis in cancer cells. Do they also prime the immune system resulting in long-term protection against cancer? Planta Medica, 78, 349-353. doi:10.1055/s-0031-1298149
[26]	Chataing, B., Concep-cion, J.L., Buitrago de Cristancho, N. and Usubillaga, A. (1996) Clinical study of the effectiveness of extracts al-kaloids obtained of the fruits of Solanum americanum miller on herpes simplex, herpes two zoster and genital herpes., 32, 18-25.
[27]	Thorne, H.V., Clarke, G.F. and Skuce, R. (1985) The inactivation of herpes simplex virus by some Solanaceae glycoalkaloids. Antivirus Re-search, 5, 335-343. doi:10.1016/0166-3542(85)90003-8
[28]	Ding, X., Zhu, F.S., Li, M. and Gao, S.G. (2012) Induction of apoptosis in human hepatoma SMMC-7721 cells by solamargine from Solanum nigrum L. Journal of Ethnopharmacology, 39, 599-604. doi:10.1016/j.jep.2011.11.058
[29]	Li, X., Zhao, Y., Ji, M., Liu, S.S., Cui, M. and Lou, H.X. (2011) Induction of actin disruption and downregulation of HER2, and en-hancement of cytotoxicity using epirubicin in NSCLC cells. Molecular Nutrition Research, 51, 999-1005.
[30]	Cham, B.E. (2007) Review article. So-lasodine rhamnosyl glycosides specifically bind cancer cell receptors and induce apoptosis and necrosis. Treatment for skin cancer and hope for internal cancers. Research Journal of Biological Sciences, 2, 503-514.
[31]	Cham, B.E. (1994) Solasodine glycosides as anti-cancer agents: Pre-clinical and clinical studies. Asia Pacific Journal of Pharmacology, 9, 113-118.
[32]	Cham, B.E., Daunter, B. and Evans, R. (1991) Topical treatment of malignant and premalignant skin cancers by very low concentrations of a standard mixture of solasodine glycosides. Cancer Letters, 59, 183-192. doi:10.1016/0304-3835(91)90140-D
[33]	Cham, B.E. (2011) Topical solasodine rhamnosyl glycosides derived from the eggplant treats large skin cancers: Two case reports. International Journal of Clinical Medicine, 2, 473-477. doi:10.4236/ijcm.2011.24080
[34]	Tavares, D.C., Munari, C.C., Araujo, M.G., Beltrame, M.C., Fur-tado, M.H., Goncalves, C.C., Tiossi, R.F., Bastos, J.K., Cunha, W.R. and Veneziani, R.C. (2011) Antimutagenic potential of Solanum lycocarpum against induction of chromosomal aberrations in V79 and micronuclei in mice by doxorubicin. Planta Medica, 77, 1489-1494. doi:10.1055/s-0030-1270886
[35]	Tang, Z., Zhang, Y., Li, N., Xu, L., Zhao, B., Xiao, W., Wang, Z. and Bi, Y. (2011) Extraction, purification technology and antineoplastic effects of solamargine. Zhongguo Zhong Yao Za Zhi, Journal of Chinese Material Medicine, 36, 2192-2195.
[36]	Wu, C.H., Liang, C.H., Shiu, L.Y., Chang, L.C., Lin, T.S., Lan, C.E.R., Tsai, J.C., Wong, T.W., Wei, K.J., Lin, T.K., Chang, N.S. and 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, 83-92.
[37]	Millward, M., Powell, A., Daly, P., Tyson, R., Ferguson, R. and Carter, S. (2006) Results of phase I clinical trials of coramsine in patients with advanced solid tumours. Journal of Clinical Oncology, 24, 2070.
[38]	Millward, M., Powell, A., Tyson, S., Daly, P., Ferguson, R. and Carter, S. (2005) Phase I trial of coram-sine (SBP002) in patients with advanced solid tumours. Journal of Clinical Oncology, 23, 3105.
[39]	Cham, B.E. (2008) Cancer intralesion chemotherapy with solasodine rhamnosyl glycosides. Research Journal of Biological Science, 3, 1008-1017.
[40]	Cham, B.E. (2012) Intralesion and Curaderm BEC5 topical combination therapies of solasodine rhamnosyl glycosides derived from the eggplant or devil’s apple result in a rapid removal of large skin cancers. Methods of treatment compared. International Journal of Clinical Medicine, 3, 115-124.
[41]	Cham, B.E. (2013) Inspired by nature, proven by science. The new generation cancer treatment that causes cancer cells to commit suicide. Submit-ted.
[42]	Cham, B.E. and Meares, M.M. (1987) Gly-coalkaloids from Solanum sodomaeum L. are effective in the treatment of skin cancers in man. Cancer Letters, 36, 111-118. doi:10.1016/0304-3835(87)90081-4
[43]	Cham, B.E., Daunter, B. and Evans, R. (1991) Topical treatment of malignant and premalignant skin cancers by very low concentrations of a standard mixture of solasodine gly-cosides. Cancer Letters, 59, 183-192. doi:10.1016/0304-3835(91)90140-D
[44]	Cham, B.E. (2013) Solasodine glycosides: A topical therapy for ac-tinic keratosis. A single-blind, randomized, place-bo-controlled, parallel group study. Submit-ted.
[45]	Punjabi, S., Cook, L.J., Kersey, P., Marks R. and Cerio, R. (2008) Solasodine glycoalkaloids: A novel topical therapy for basal cell carcinoma. A double-blind, randomized, placebo-controlled, parallel group, multicentre study. International Journal of Dermatology, 47, 78-82.
[46]	Cham, B.E. (2007) Solasodine rhamnosyl glycosides in a cream formulation is effective for treating large and troublesome skin cancers. Research Journal of Biological Sciences, 2, 749-761.
[47]	Cham, B.E. (2011) Topical solasodine rhamnosyl glycosides derived from the eggplant treats large skin cancers: Two case reports. International Journal of Clinical Medicine, 2, 473-477. doi:10.4236/ijcm.2011.24080
[48]	Cham, B.E. (2007) Solasodine rhamnosyl glycosides specifically bind cancer cell receptors and induce apoptosis and necrosis. Treatment for skin cancer and hope for internal cancers. Research Journal of Biological Sciences, 2, 503-514.
[49]	Chase, T.R. (2011) Curaderm BEC5 for skin cancers, is it? An overview. Journal of Cancer Therapy, 2, 728-745. doi:10.4236/jct.2011.25099
[50]	Goldberg, L.H., Landau, J.M., Moody, M.N. and Vergilis-Kalner, I.J. (2011) Treatment of Bowen’s disease on the penis with low con-centration of a standard mixture of solasodine glycosides and liquid nitrogen. Dermatologic Surgery, 37, 858-861. doi:10.1111/j.1524-4725.2011.02014.x