Solasodine Glycosides: A Topical Therapy for Actinic Keratosis. A Single-Blind, Randomized, Placebo-Controlled, Parallel Group Study with Curaderm<sup>BEC5</sup> — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Solasodine Glycosides: A Topical Therapy for Actinic Keratosis. A Single-Blind, Randomized, Placebo-Controlled, Parallel Group Study with Curaderm<sup>BEC5</sup>
Australasian Institute of Medical Research, Brisbane, Australia.
1 Australasian Institute of Medical Research, Brisbane, Australia.
Background: Untreated actinic keratosis can advance to squamous cell carcinoma, which in turn is associated with a risk of metastasis. Current treatments for actinic keratosis have many shortcomings. This communication describes the efficacy and safety of a topical cream therapy, Curaderm BEC5 , containing solasodine glycosides (0.005%) for actinic keratosis. Methods: Randomly assigned patients with actinic keratosis on the face, trunk or extremities received so -lasodine glycosides cream (Curaderm BEC5 ) or placebo (vehicle) that was self-applied to the lesions and covered with an occlusive dressing (micropore) twice daily for 3 consecutive days. Complete clearance and local reactions were as-sessed at 56 days with follow-up periods of 6 months and 1 year. Results: The rate of complete clearance at day 56 was higher with solasodine glycosides than with placebo (92% vs. 38%, P < 0.001). The absolute success rates after 1 year follow-up were 82% for solasodine glycosides and 18% for placebo. No differences in local reactions were obtained when solasodine glycosides and placebo were compared. Local reactions in both groups peaked at days 2 and 3 with local pain as the major event. The pain associated with treatments lasted approximately 10 minutes after application of solasodine glycosides and placebo. Complete reepithelialization occurred two weeks after treatment. Adverse events were generally mild to moderate in intensity and resolved without sequelae. Conclusions: Solasodine glycosides cream applied topically twice daily with a dressing for 3 days is effective for the treatment of actinic keratoses.
E. Stockfleth, C. Ferrandix, J. J. Grob, I. Leigh, H. Pehumberger and H. Kerl, “Development of a Treatment Algorithim for Actinic Keratoses: A European Consensus,” European Journal Dermatology, Vol. 18, No. 6, 2008, pp. 651-659.
N. Krawtchenko, J. Roewert-Huber, M. Ulrich, I. Mann, W. Sterry and E. Stockfleth, “A Randomized Study of Topical 5% Imiquimod vs. Topical 5-Fluorouracil vs. Cryosurgery in Immunocompetent Patients with Actinic Keratoses: A Comparison of Clinical and Histological Outcomes Including 1-Year Follow-Up,” British Journal Dermatology, Vol. 157 Supplementary 2, 2007, pp. 34-40.
S. R. Feldman and A. B. Fleishcer Jr., “Progression of Actinic Keratosis to Squamous Cell Carcinoma Revisited: Clinical and Treatment Implications,” Cutis, Vol. 84, No. 4, 2011, pp. 201-207.
T. R. Chase, “CuradermBEC5 for Skin Cancers, Is It? An Overview,” Journal Cancer Therapy, Vol. 2, No. 5, 2011, pp. 728-745. doi:10.4236/jct.2011.25099
B. E. Cham, M. Gilliver and L. Wilson, “Antitumour Effects of Glycoalkaloids Isolated from Solanum sodomaeum L.,” Planta Medica, Vol. 53, No. 1, 1987, pp. 34-36. doi:10.1055/s-2006-962612
B. E. Cham and B. Daunter, “Solasodine Glycosides. Selective Cytotoxicity for Cancer Cells and Inhibition of Cytotoxicity by Rhamnose in Mice with Sarcoma 180,” Cancer Letters, Vol. 55, No. 3, 1990, pp. 221-225. doi:10.1016/0304-3835(90)90122-E
M. Freedman, K. R. Lee, H. J. Kim, I. S. Lee and N. Kozukue, “Anticarcinogenic Effects of Glycoalkaloids from Potatoes Against Human Cervical, Liver, Lymphoma and Stomach Cancer Cells,” Journal Agriculture Food Chemistry, Vol. 53, No. 15, 2005, pp. 6162-6169. doi:10.1021/jf050620p
K. W. Kuo, S. H. Hsu, Y. P. Li, W. L. Lin, L. F. Liu, L. C. Chang, C. C. Lin, C. N. Lin and H. M. Sheu, “Anticancer Activity Evaluation of the Solanum Glycoalkaloid Solamargine. Triggering Apoptosis in Human Hepatoma Cells,” Biochemical Pharmacology, Vol. 60, No. 2, 2000, pp. 865-1873. doi:10.1016/S0006-2952(00)00506-2
K. W. Kuo and C. N. Lin, “Pharmacological Composition for Treating Cancer Cells,” US Patent: 214,803, 1999.
K. R. Lee, N. Kozukue, J. S. Han, J. H. Park, E. Y. Chang, E. J. Back, J. D. Chang and M. Friedman, “Glycoalkaloids and Metabolites Inhibit the Growth of Human Colon (HT29) and Liver (HepG2) Cancer Cells,” Journal Agriculture Food Chemistry, Vol. 52, No. 10, 2004, pp. 2832-2839. doi:10.1021/jf030526d
C. H. Liang, L. F. Liu, L. Y. Shiu, Y. S. Huang, L. C. Chang and K. W. Kuo, “Action of Solamargine on TNFs and Cisplatin-Resistant Human Lung Cancer Cells,” Biochemical Biophysical Research Communication, Vol. 322, No. 3, 2004, pp. 751-758. doi:10.1016/j.bbrc.2004.07.183
C. H. Liang, L. Y. Shiu, L. C. Chang, H. M. Sheu and K. W. Kuo, “Solamargine Upregulation of Fas, Downregulation of HER 2, and Enhancement of Cytotoxicity Using Epirubicin in NSCLC Cells,” Molecular Nutrition Food Research, Vol. 51, No. 8, 2007, pp. 999-1005. doi:10.1002/mnfr.200700044
L. F. Liu, C. H. Liang, L. Y. Shiu, W. L. Lin, C. C. Lin and K. W. Kuo, “Action of Solamargine on Human Lung Cancer Cells-Enhancement of the Susceptibility of Cancer Cells to TNFs,” FEBS Letters, Vol. 577, No. 1-2, 2004, pp. 67-74. doi:10.1016/j.febslet.2004.09.064
M. Millward, A. Powell, P. Daly, S. Tyson, R. Ferguson and S. Carter, “Results of Phase I Clinical Trials of Coramsine in Patients with Advanced Solid Tumors,” Journal Clinical Oncology, Vol. 2, No. 18, 2006, p. 2070.
T. Nakamura, C. Komori, Y. Lee, F. Hashinoto, S. Yahara, T. Nohara and A. Ejina, “Cytotoxic Activities of Solanum Steroidal Glycosides,” Biology Biopharmacy Bulletin, Vol. 19, No. 4, 1996, pp. 564-566. doi:10.1248/bpb.19.564
K. Ono, S. O. Kin and J. Han, “Susceptibility of Lysosomes to Rupture Is a Determinant for Plasma Membrane Disruption in Tumor Necrosis Factor Alpha-Indued Cell Death,” Molecular Cell Biology, Vol. 23, No. 2, 2003, pp. 665-676. doi:10.1128/MCB.23.2.665-676.2003
M. Ono, K. Nishimura, K. Suzuki, T. Fukushima, K. Igoshi, H. Yoshimitsu, T. Ikeda and T. Nohara, “Steroidal Glycosides from the Underground Parts of Solanum Sodomaeum,” Chemical Pharmacy Bulletin, Vol. 54, No. 2, 2006, pp. 230-233. doi:10.1248/cpb.54.230
J. G. Roddick, A. L. R?renber and M. Weissenber, “Membrane-Disrupting Properties of the Steroidal Glycoalkaloids Solasonine and Solamargine,” Phyto Chemistry, Vol. 29, No. 5, 1990, pp. 1513-1518. doi:10.1016/0031-9422(90)80111-S
P. Vijayan, K. S. Vinod, S. A. Dhanaraj, S. Badami and B. Suresh, “In Vitro Cytotoxicity and Anti-Tumour Properties of the Total Alkaloid Fraction of Unripe Fruits of Solanum Pseudocapsicum,” Pharmacology Biology, Vol. 40, No. 6, 2002, pp. 456-460. doi:10.1076/phbi.40.6.456.8444
B. E. Cham, “Solasodine Rhamnosyl Glycosides Specifically Bind Cancer Cell Receptors and Induce Apoptosis and Necrosis. Treatment for Skin Cancer and Hope for Internal Cancers,” Research Journal Biological Science, Vol. 2, No. 7, 2007, pp. 503-514.
B. E. Cham, “Solasodine Rhamnosyl Glycosides in a Cream Formulation Is Effective for Treating Large and Troublesome Skin Cancers,” Research Journal Biological Science, Vol. 2, No. 7, 2007, pp. 749-761.
B. E. Cham, “Cancer Intralesion Chemotherapy with Solasodine Rhamnosyl Glycosides,” Research Journal Biological Science, Vol. 3, No. 9, 2008, pp. 1008-1017.
L. Y. Shiu, L. C. Chang, C. H. Liang, Y. S. Huang, H. M. Sheu and K. W. Kuo, “Solamargine Induces Apoptosis and Sensitizes Breast Cancer Cells to Cisplatin,” Food Chemical Toxicology, Vol. 45, No. 11, 2007, pp. 2155-2164. doi:10.1016/j.fct.2007.05.009
Google Search, “Solamargine Anticancer,”
B. E. Cham and T. R. Chase, “Solasodine Rhamnosyl Glycosides Cause Apoptosis in Cancer Cells, Do They Also Prime the Immune System Resulting in Long Term Protection against Cancer?” Planta Medica, Vol. 78, 2012, pp. 349-353. doi:10.1055/s-0031-1298149
R. G. Van der Most, R. Himbeck, S. Aarens, S. J. Carter, I. Larma, C. Robinson, A. Currice and R. A. Lake, “Antitumor Efficacy of the Novel Chemotherapeutic Agent Coramsine Is Potentiated by Cotreatment with CpG-Containing Oligodeoxynucleotides,” Journal Immunology, Vol. 29, No. 2, 2006, pp. 134-142.
B. Daunter and B. E. Cham, “Solasodine Glycosides. In Vitro Preferential Cytotoxicity for Human Cancer Cells,” Cancer Letters, Vol. 55, No. 3, 1990, pp. 209-220. doi:10.1016/0304-3835(90)90121-D
X. Li, Y. Zhao, W. K. K. Wu, S. Liu, M. Cui and H. Lou, “Solamargine Induces Apoptosis Associated with p53 Transcription-Dependent and Transcription-Independent Pathways in Human Osteosarcoma U20S Cells,” Life Science, Vol. 88, No. 7-8, 2011, pp. 314-321. doi:10.1016/j.lfs.2010.12.006
B. E. Cham, “Solasodine Glycosides as Anti-Cancer Agents: Pre-Clinical and Clinical Studies,” Asia Pacific Journal Pharmacology, Vol. 9, No. 2, 1994, pp. 113-118.
L. Y. Shiu, C. H. Liang, Y. S. Huang, H. M. Sheu and K. W. Kuo, “Downregulation of HER2/neu Receptor by Solamargine Enhances Anticancer Drug-Mediated Cytotoxicity in Breast Cancer Cells with High-Expressing HER2/ neu,” Cell Biology Toxicology, Vol. 24, No. 1, 2008, pp. 1-10.
L. Sun, Y. Zhao, H. Yuan, X. Li, A. Cheng and H. Lou, “Solamargine, a Steroidal Alkaloid Glycoside, Induces Oncosis in Human K562 Leukemia and Squamous Cell Carcinoma KB Cells,” Cancer Chemotherapy Pharmacology, Vol. 65, No. 4, 2010, pp. 1125-1130. doi:10.1007/s10565-007-9010-5
B. E. Cham, B. Daunter and R. Evans, “Topical Treatment of Malignant and Premalignant Skin Cancers by Very Low Concentrations of a Standard Mixture of Solasodine Glycosides,” Cancer Letters, Vol. 59, No. 3, 1991, pp. 183-192. doi:10.1016/0304-3835(91)90140-D
B. E. Cham and H. M. Meares, “Glycoalkaloids from Solanum Sodomaeum L. Are Effective in the Treatment of Skin Cancers in Man,” Cancer Letters, Vol. 36, No. 2, 1987, pp. 111-118. doi:10.1016/0304-3835(87)90081-4
S. Punjabi, L. J. Cook, P. Kersey, R. Marks and R. Cerio, “Solasodine Glycoalkaloids: A Novel Topical Therapy for Basal Cell Carcinoma. A Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multicentre Study,” International Journal Dermatology, Vol. 47, No. 1, 2008, pp. 78-82. doi:10.1111/j.1365-4632.2007.03363.x
B. E. Cham, “Topical Solasodine Rhamnosyl Glycosides Derived from the Eggplant Treats Large Skin Cancers: Two Case Reports,” International Journal Clinical Medicine, Vol. 2, No. 4, 2011, pp. 473-477.
L. H. Goldberg, J. M. Landau, M. N. Moody and I. J. Vergilis-Kalner, “Treatment of Bowen’s Disease on the Penis with Low Concentration of a Standard Mixture of Solasodine Glycosides and Liquid Nitrogen,” Dermatologic Surgery, Vol. 37, No. 6, 2011, pp. 858-861. doi:10.1111/j.1524-4725.2011.02014.x
B. E. Cham and L.Wilson, “HPLC of Glycoalkaloids from Solanum Sodomaeum,” Planta Medica, Vol. 53, No. 1, 1987, pp. 34-36. doi:10.1055/s-2006-962612
B. E. Cham, “Intralesion and CuradermBEC5 Topical Combination Therapies of Solasodine Rhamnosyl Glycosides Derived from the Eggplant or Devil’s Apple Result in Rapid Removal of Large Skin Cancers. Methods of Treatment Compared,” International Journal Clinical Medicine, Vol. 3, No. 2, 2012, pp. 115-124. doi:10.4236/ijcm.2012.32024
B. E. Cham, “Drug Therapy: Solamargine and Other Solasodine Rhamnosyl Glycosides as Anticancer Agents,” Modern Chemotherapy, in Press.
J. K. Rivers, J. Arlette, N. Shear, L. Guenther, N. Carey and Y. Poulin, “Topical Treatment of Actinic Keratoses with 3.0% Diclofenac in 2.5% Hyaluran Gel,” British Journal Dermatology, Vol. 146, No. 1, 2002, pp. 94-100. doi:10.1046/j.1365-2133.2002.04561.x
J. E. Wolf Jr., J. R. Taylor, E. Tschen and S. Kang, “Topical 3.0% Diclofenac in 2.5% Hyaluran Gel in the Treatment of Actinic Keratoses,” International Journal Dermatology, Vol. 40, No. 11, 2001, pp. 709-713. doi:10.1046/j.1365-4362.2001.01324.x
M. Lebwohl, S. Dinehart, D. Whiting, et al., “Imiquimod 5% Cream for the Treatment of Actinic Keratosis: Results from Two Phase III, Randomized, Double-Blind Parallel Group, Vehicle Controlled Trials,” Journal American Academy Dermatology, Vol. 50, No. 5, 2004, pp. 714-721. doi:10.1016/j.jaad.2003.12.010
N. Swanson, W. Abramovits, B. Breman, J. Kulp, D. S. Rigel and S. Levy, “Imiquimod 2.5% and 3.75% for the Treatment of Actinic Keratoses: Results of Two Placebo-Controlled Studies of Daily Application to the Face and Balding Scalp for Two 2-Week Cycles,” Journal American Academy Dermatology, Vol. 62, No. 4, 2010, pp. 582-590. doi:10.1016/j.jaad.2009.07.004
J. Weiss, A. Menter, O. Hevia, et al., “Effective Treatment of Actinic Keratosis with 0.5% Fluorouracil Cream for 1, 2 or 4 Weeks,” Cutis, Vol. 70, Suppl. 2, 2002, pp. 22-29.
B. Yentzer, J. Hick, L. Williams, et al., “Adherence to a Topical Regimen of 5-Fluorouracil, 0.5% Cream for the Treatment of Actinic Keratoses,” Academy Dermatology, Vol. 145, No. 2, 2009, pp. 203-205.
“Highlights of Prescribing Information—Picato Gel,” 2012. www.leopharma.us/Files/Billeder/ LEO_local_images/LEO-Pharma.US/Releases/ Picato%20PI.pdf
C. H. Wu, C. H. Liang, L. Y. Shiu, L. C. Chang, T. S. Lin, C. E. R. Lan, J. C. Tsai, T. W. Wong, K. J. Wei, T. K. Lin, N. S. Chang and H. M. Sheu, “Solanum Incanum Extract (SR-T100) Induces Human Cutaneous Squamous Cell Carcinoma Apoptosis through Modulating Tumor Necrosis Factor Receptor Signaling Pathway,” Journal Dermatology Science, Vol. 63, No. 2, 2011, pp. 83-92.
T. M. Housman, S. R. Feldman, P. M. Williford, A. B. Fleischer Jr., N.D. Goldman, M. Acostamadiedo and G. J. Chen, “Skin Cancer Is Among the Most Costly of All Cancers to Treat for the Medicare Population,” Journal American Academy Dermatology, Vol. 48, No. 3, 2003, pp. 425-429. doi:10.1067/mjd.2003.186