Background Solamargine （SM）, a steroidal glycoalkaloid isolated from the Chinese herb Solanum incanum, has been shown to inhibit the growth of some cancer cell lines and induce significant apoptosis. However, the ef...Background Solamargine （SM）, a steroidal glycoalkaloid isolated from the Chinese herb Solanum incanum, has been shown to inhibit the growth of some cancer cell lines and induce significant apoptosis. However, the effects of SM on multidrug-resistant （MDR） cells and the molecular mechanisms involved are poorly understood. The purpose of this study was to evaluate the anti-MDR effects of SM and the associated mechanisms in MDR K562/A02 cells. Methods The cytotoxicity of SM was measured by 3-（4,5-dimethylthiazol）-2,5-diphenyltetrazolium bromide （MTT） assay. The 14＇,6-diamidino-2-phenylindole （DAPi） nuclear staining and flow cytometry were used to detect SM-induced apoptosis. The mRNA expression of P-glycoprotein （P-gp） was investigated by real-time PCR （RT-PCR）. Western blotting was used to determine the expression of Bcl-2, Bax, and actin. The changes in the morphology of actin were examined with immunofluorescence staining. Results MTT results showed that SM effectively killed the MDR sublines K562/A02, KB/VCR, and H460/paclitaxel （Taxol）, and their parental cell lines K562, KB, and H460 to an equivalent or more sensitive degree. Based on the results by flow cytometry and immunostaining, the pro-apoptotic effects of SM were observed in MDR K562/A02 cells. Furthermore, the RT-PCR results showed that SM induced the downregulation of MDR1 mRNA. In addition, the expression of P-gp and actin was decreased in the SM-treated cells, as measured by western blotting and immunostaining. Conclusions These results demonstrate that SM effectively triggers apoptosis in MDR tumor cells, which is associated with actin disruption and downregulation of MDR1 expression. This compound may merit further investigation as a Potential therapeutic aaent that bvDasses the MDR mechanism for the treatment of MDR tumors.展开更多
Solasodine rhamnosyl glycosides (SRGs) are chemotherapeutic agents for the treatment of cancer. SRGs in a cream formulation, CuradermBEC5, is very effective for the treatment of nonmelanoma skin cancers with excellent...Solasodine rhamnosyl glycosides (SRGs) are chemotherapeutic agents for the treatment of cancer. SRGs in a cream formulation, CuradermBEC5, is very effective for the treatment of nonmelanoma skin cancers with excellent cosmetic end results. Intralesion injection of SRGs successfully dispose of very large tumours in animals without any clinical adverse effects. The mode of action of SRGs is by apoptosis. In this study, it is shown that small to large basal cell carcinomas are effectively treated only with topical application of CuradermBEC5. Here it is reported for the first time that combination of intralesion SRG injection and topical application with CuradermBEC5 in humans reduces the treatment time period by more than half when compared with topical application as the sole treatment regime. Two intralesion injections of very low doses of SRGs rapidly and effectively remove a large melanoma on a horse. If rapid removal of large troublesome skin cancers is required then this can be achieved by intralesion and topical treatments. Intralesion or combination therapy with SRGs may have some applications for melanomas in situ such as lentigo maligna.展开更多
The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-inv...The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-invasive treatments like Curaderm have been developed, leading to improved quality of life for patients. Excipients, previously considered inactive ingredients, play a crucial role in enhancing the performance of topical formulations. The development of Curaderm emphasizes the importance of understanding the interactions between active ingredients, excipients, and the biological system to create effective and affordable pharmaceutical formulations. The systematic approach taken in the development of Curaderm, starting from the observation of the anticancer activity of natural solasodine glycosides and progressing through toxicological and efficacy studies in cell culture, animals, and humans, has provided insights into the pharmacokinetics and pharmacodynamics of solasodine glycosides. It is crucial to determine these pharmacological parameters within the skin’s biological system for maximal effectiveness and cost-effectiveness of a skin cancer treatment. Curaderm, as a topical treatment for nonmelanoma skin cancer, offers benefits beyond those obtained from other topical treatments, providing hope for improved quality of life for patients.展开更多
To study the effect of the sugar chains in glycoalkaloids against cancer cells, 6-0-sulfated solamargine and acidcatalyzed hydrolytic products of α-solamargine and α-solasonine were prepared. The sulfation at 0-6 of...To study the effect of the sugar chains in glycoalkaloids against cancer cells, 6-0-sulfated solamargine and acidcatalyzed hydrolytic products of α-solamargine and α-solasonine were prepared. The sulfation at 0-6 of solamargine was proceeded in five steps. The 6-OH group was first selectively protected with DMT-Cl, and then the secondary hydroxyl groups on the sugar ring were acetylated. After the protective group DMTr was removed, the free 6-OH group was sulfated. Finally, the acetyl groups were removed to give 6-0-sulfated solamargine in a good yield. The hydrolyses of solamargine and solasonine were performed in diluted hydrogen chlorede. Three and two hydrolyzed products were obtained from solamargine and solasonine, respectively. The antiproliferative activities against HCT-8 tumor cells of two glycoalkaloids and their derivaties were examined via a MTT assay. The results show that α-solamargine and α-solasonine exhibit strong cytotoxic activities with an IC50 of 10. 63 and 11.97 μmol/L, respectively, wheras their derivaties seem to be less activities.展开更多
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 communicatio...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, CuradermBEC5, 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 (CuradermBEC5) 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.展开更多
Plant-derived BEC with its main component solamargine possesses anticancer activities via its effect on a variety of biological pathways in a wide range of human cancer cells. High cure rates with BEC therapy have bee...Plant-derived BEC with its main component solamargine possesses anticancer activities via its effect on a variety of biological pathways in a wide range of human cancer cells. High cure rates with BEC therapy have been obtained in animals with deadly cancers, and, in humans with terminal cancers promising results have been reported. At a clinical level, optimal concentrations of BEC have been established in a topical cream formulation Curaderm, for effective removal of skin cancers, but optimal concentrations of BEC have not been reported for other cancers. The objective of this study was to determine whether combination therapy of Cisplatin with BEC would result in synergism using cure rates as end points. BEC on its own cures Sarcoma 180 in mice, whereas, Cisplatin on its own has no effect on Sarcoma 180 activity. A combination of BEC and Cisplatin shows synergism, resulting in higher cure rates than BEC and Cisplatin at comparable individual concentrations.展开更多
<strong>Background:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> There is ample evidence...<strong>Background:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> There is ample evidence to support the safety and efficacy of the topical anticancer cream Curaderm in the treatment of non-melanoma skin cancers. Curaderm contains the natural glycoalkaloid solamargine in the form of BEC, which has been established as a novel antineoplastic agent. BEC is the initials of the inventor of the described technology. It is known that BEC expresses anti-melanoma properties in cell culture and animals. Because of potential metastasis, clinical work with BEC on melanoma was stalled. However, recent studies show that BEC has anti-metastatic properties and this, together with currently better understanding of the mode of anti-cancer actions of BEC</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> has led to the treatment of a patient who refused to have surgery for her clinically diagnosed stage II melanoma. </span><b><span style="font-family:Verdana;">Treatment: </span></b><span style="font-family:Verdana;">A 67-year woman had a birthmark that developed into a clinically diagnosed stage II melanoma and was treated with topical application of Curaderm twice daily for 7 weeks. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> The pattern of response of the melanoma to Curaderm therapy was similar to that observed when basal cell carcinoma is treated with Curaderm. The melanoma responded rapidly to the treatment and in 7 weeks the lesion was removed with no demonstrable side effects. The cosmetic end result was very acceptable. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> The clinical resolution of the melanoma with Curaderm pharmacotherapy conforms to the cell culture and animal obse展开更多
基金This work was supported by the grants from the National Natural Science Foundation of China （No. 81072660）, the Shandong Provincial Natural Science Foundation （No. ZR2009CMI22） and the Shandong Provincial Doctoral Foundation （No. BS2009YY016）.
文摘Background Solamargine （SM）, a steroidal glycoalkaloid isolated from the Chinese herb Solanum incanum, has been shown to inhibit the growth of some cancer cell lines and induce significant apoptosis. However, the effects of SM on multidrug-resistant （MDR） cells and the molecular mechanisms involved are poorly understood. The purpose of this study was to evaluate the anti-MDR effects of SM and the associated mechanisms in MDR K562/A02 cells. Methods The cytotoxicity of SM was measured by 3-（4,5-dimethylthiazol）-2,5-diphenyltetrazolium bromide （MTT） assay. The 14＇,6-diamidino-2-phenylindole （DAPi） nuclear staining and flow cytometry were used to detect SM-induced apoptosis. The mRNA expression of P-glycoprotein （P-gp） was investigated by real-time PCR （RT-PCR）. Western blotting was used to determine the expression of Bcl-2, Bax, and actin. The changes in the morphology of actin were examined with immunofluorescence staining. Results MTT results showed that SM effectively killed the MDR sublines K562/A02, KB/VCR, and H460/paclitaxel （Taxol）, and their parental cell lines K562, KB, and H460 to an equivalent or more sensitive degree. Based on the results by flow cytometry and immunostaining, the pro-apoptotic effects of SM were observed in MDR K562/A02 cells. Furthermore, the RT-PCR results showed that SM induced the downregulation of MDR1 mRNA. In addition, the expression of P-gp and actin was decreased in the SM-treated cells, as measured by western blotting and immunostaining. Conclusions These results demonstrate that SM effectively triggers apoptosis in MDR tumor cells, which is associated with actin disruption and downregulation of MDR1 expression. This compound may merit further investigation as a Potential therapeutic aaent that bvDasses the MDR mechanism for the treatment of MDR tumors.
文摘Solasodine rhamnosyl glycosides (SRGs) are chemotherapeutic agents for the treatment of cancer. SRGs in a cream formulation, CuradermBEC5, is very effective for the treatment of nonmelanoma skin cancers with excellent cosmetic end results. Intralesion injection of SRGs successfully dispose of very large tumours in animals without any clinical adverse effects. The mode of action of SRGs is by apoptosis. In this study, it is shown that small to large basal cell carcinomas are effectively treated only with topical application of CuradermBEC5. Here it is reported for the first time that combination of intralesion SRG injection and topical application with CuradermBEC5 in humans reduces the treatment time period by more than half when compared with topical application as the sole treatment regime. Two intralesion injections of very low doses of SRGs rapidly and effectively remove a large melanoma on a horse. If rapid removal of large troublesome skin cancers is required then this can be achieved by intralesion and topical treatments. Intralesion or combination therapy with SRGs may have some applications for melanomas in situ such as lentigo maligna.
文摘The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-invasive treatments like Curaderm have been developed, leading to improved quality of life for patients. Excipients, previously considered inactive ingredients, play a crucial role in enhancing the performance of topical formulations. The development of Curaderm emphasizes the importance of understanding the interactions between active ingredients, excipients, and the biological system to create effective and affordable pharmaceutical formulations. The systematic approach taken in the development of Curaderm, starting from the observation of the anticancer activity of natural solasodine glycosides and progressing through toxicological and efficacy studies in cell culture, animals, and humans, has provided insights into the pharmacokinetics and pharmacodynamics of solasodine glycosides. It is crucial to determine these pharmacological parameters within the skin’s biological system for maximal effectiveness and cost-effectiveness of a skin cancer treatment. Curaderm, as a topical treatment for nonmelanoma skin cancer, offers benefits beyond those obtained from other topical treatments, providing hope for improved quality of life for patients.
基金Supported by the National Natural Science Foundation of China(No30570417)the Natural Science Foundation of JilinProvince(No20040546)
文摘To study the effect of the sugar chains in glycoalkaloids against cancer cells, 6-0-sulfated solamargine and acidcatalyzed hydrolytic products of α-solamargine and α-solasonine were prepared. The sulfation at 0-6 of solamargine was proceeded in five steps. The 6-OH group was first selectively protected with DMT-Cl, and then the secondary hydroxyl groups on the sugar ring were acetylated. After the protective group DMTr was removed, the free 6-OH group was sulfated. Finally, the acetyl groups were removed to give 6-0-sulfated solamargine in a good yield. The hydrolyses of solamargine and solasonine were performed in diluted hydrogen chlorede. Three and two hydrolyzed products were obtained from solamargine and solasonine, respectively. The antiproliferative activities against HCT-8 tumor cells of two glycoalkaloids and their derivaties were examined via a MTT assay. The results show that α-solamargine and α-solasonine exhibit strong cytotoxic activities with an IC50 of 10. 63 and 11.97 μmol/L, respectively, wheras their derivaties seem to be less activities.
文摘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, CuradermBEC5, 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 (CuradermBEC5) 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.
文摘Plant-derived BEC with its main component solamargine possesses anticancer activities via its effect on a variety of biological pathways in a wide range of human cancer cells. High cure rates with BEC therapy have been obtained in animals with deadly cancers, and, in humans with terminal cancers promising results have been reported. At a clinical level, optimal concentrations of BEC have been established in a topical cream formulation Curaderm, for effective removal of skin cancers, but optimal concentrations of BEC have not been reported for other cancers. The objective of this study was to determine whether combination therapy of Cisplatin with BEC would result in synergism using cure rates as end points. BEC on its own cures Sarcoma 180 in mice, whereas, Cisplatin on its own has no effect on Sarcoma 180 activity. A combination of BEC and Cisplatin shows synergism, resulting in higher cure rates than BEC and Cisplatin at comparable individual concentrations.
文摘<strong>Background:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> There is ample evidence to support the safety and efficacy of the topical anticancer cream Curaderm in the treatment of non-melanoma skin cancers. Curaderm contains the natural glycoalkaloid solamargine in the form of BEC, which has been established as a novel antineoplastic agent. BEC is the initials of the inventor of the described technology. It is known that BEC expresses anti-melanoma properties in cell culture and animals. Because of potential metastasis, clinical work with BEC on melanoma was stalled. However, recent studies show that BEC has anti-metastatic properties and this, together with currently better understanding of the mode of anti-cancer actions of BEC</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> has led to the treatment of a patient who refused to have surgery for her clinically diagnosed stage II melanoma. </span><b><span style="font-family:Verdana;">Treatment: </span></b><span style="font-family:Verdana;">A 67-year woman had a birthmark that developed into a clinically diagnosed stage II melanoma and was treated with topical application of Curaderm twice daily for 7 weeks. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> The pattern of response of the melanoma to Curaderm therapy was similar to that observed when basal cell carcinoma is treated with Curaderm. The melanoma responded rapidly to the treatment and in 7 weeks the lesion was removed with no demonstrable side effects. The cosmetic end result was very acceptable. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> The clinical resolution of the melanoma with Curaderm pharmacotherapy conforms to the cell culture and animal obse
