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Dose-response on the chemopreventive effects of sarcophine-diol on UVB-induced skin tumor development in SKH-1 hairless mice.

Guillermo RF, Zhang X, Kaushik RS, Zeman D, Ahmed SA, Khalifa S, Fahmy H, Dwivedi C - Mar Drugs (2012)

Bottom Line: Weight gain and any signs of toxicity were also closely monitored.The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose.The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA. Ruth.Guillermo@sdstate.edu

ABSTRACT
Sarcophine-diol (SD) is a lactone ring-opened analogue of sarcophine. It has shown chemopreventive effects on chemically-induced skin tumor development in female CD-1 mice, as well as in a UVB-induced skin tumor development model in hairless SKH-1 mice at a dose of 30 μg SD applied topically and 180 mJ/cm(2) UVB. The objective of this study was to determine the dose-response on the chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB radiation dose of 30 mJ/cm(2). This UVB dose better represents chronic human skin exposure to sunlight leading to skin cancer than previous studies applying much higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into five groups. The control group was topically treated with 200 μL of acetone (vehicle), and the SD treatment groups were topically treated with SD (30 μg, 45 μg, and 60 μg dissolved in 200 μL of acetone) 1 h before UVB radiation (30 mJ/cm(2)). The last group of animals received 60 μg SD/200 μL acetone without UVB exposure. These treatments were continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a weekly basis for 27 weeks. Weight gain and any signs of toxicity were also closely monitored. Histological characteristics and the proliferating cell nuclear antigen (PCNA) were evaluated in the mice skin collected at the end of the experiment. The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose. SD reduced the number of cells positively stained with PCNA proliferation marker in mice skin. The study also showed that SD application without UVB exposure has no effect on the structure of skin. The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.

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Effects of SD treatment on tumor multiplicity in SKH-1 mice. SD pretreatment significantly (P <0.05) decreased tumor multiplicity in all groups by the end of the experiment. Each point represents mean number of tumors per mice ± SEM derived from 20 mice in each group. * Significantly different.
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marinedrugs-10-02111-f003: Effects of SD treatment on tumor multiplicity in SKH-1 mice. SD pretreatment significantly (P <0.05) decreased tumor multiplicity in all groups by the end of the experiment. Each point represents mean number of tumors per mice ± SEM derived from 20 mice in each group. * Significantly different.

Mentions: The effects of SD in tumor multiplicity (average number of tumors per mouse) are presented in Figure 3. At the 27th week, the mean number of tumors per mouse was 14, 7, 6.7, and 6.2 for the control, 30 μg, 45 μg, and 60 μg SD groups respectively. This accounts for a 50%, 52.1%, and 55.8% inhibition in tumor multiplicity for 30, 45, and 60 μg/dose respectively. This model showed even stronger SD effects than a previous study, where we found a 36% inhibition rate in tumor multiplicity with SD (30 μg/dose) as compared to acetone (UVB dose: 180 mJ/cm2) [18]. Overall, SD pre-treatment resulted in a significant (P < 0.05) reduction in tumor multiplicity in all groups. However, there were not significant differences in tumor multiplicity among the different treatment groups (SD 30, 45, 60 μg).


Dose-response on the chemopreventive effects of sarcophine-diol on UVB-induced skin tumor development in SKH-1 hairless mice.

Guillermo RF, Zhang X, Kaushik RS, Zeman D, Ahmed SA, Khalifa S, Fahmy H, Dwivedi C - Mar Drugs (2012)

Effects of SD treatment on tumor multiplicity in SKH-1 mice. SD pretreatment significantly (P <0.05) decreased tumor multiplicity in all groups by the end of the experiment. Each point represents mean number of tumors per mice ± SEM derived from 20 mice in each group. * Significantly different.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475277&req=5

marinedrugs-10-02111-f003: Effects of SD treatment on tumor multiplicity in SKH-1 mice. SD pretreatment significantly (P <0.05) decreased tumor multiplicity in all groups by the end of the experiment. Each point represents mean number of tumors per mice ± SEM derived from 20 mice in each group. * Significantly different.
Mentions: The effects of SD in tumor multiplicity (average number of tumors per mouse) are presented in Figure 3. At the 27th week, the mean number of tumors per mouse was 14, 7, 6.7, and 6.2 for the control, 30 μg, 45 μg, and 60 μg SD groups respectively. This accounts for a 50%, 52.1%, and 55.8% inhibition in tumor multiplicity for 30, 45, and 60 μg/dose respectively. This model showed even stronger SD effects than a previous study, where we found a 36% inhibition rate in tumor multiplicity with SD (30 μg/dose) as compared to acetone (UVB dose: 180 mJ/cm2) [18]. Overall, SD pre-treatment resulted in a significant (P < 0.05) reduction in tumor multiplicity in all groups. However, there were not significant differences in tumor multiplicity among the different treatment groups (SD 30, 45, 60 μg).

Bottom Line: Weight gain and any signs of toxicity were also closely monitored.The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose.The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA. Ruth.Guillermo@sdstate.edu

ABSTRACT
Sarcophine-diol (SD) is a lactone ring-opened analogue of sarcophine. It has shown chemopreventive effects on chemically-induced skin tumor development in female CD-1 mice, as well as in a UVB-induced skin tumor development model in hairless SKH-1 mice at a dose of 30 μg SD applied topically and 180 mJ/cm(2) UVB. The objective of this study was to determine the dose-response on the chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB radiation dose of 30 mJ/cm(2). This UVB dose better represents chronic human skin exposure to sunlight leading to skin cancer than previous studies applying much higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into five groups. The control group was topically treated with 200 μL of acetone (vehicle), and the SD treatment groups were topically treated with SD (30 μg, 45 μg, and 60 μg dissolved in 200 μL of acetone) 1 h before UVB radiation (30 mJ/cm(2)). The last group of animals received 60 μg SD/200 μL acetone without UVB exposure. These treatments were continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a weekly basis for 27 weeks. Weight gain and any signs of toxicity were also closely monitored. Histological characteristics and the proliferating cell nuclear antigen (PCNA) were evaluated in the mice skin collected at the end of the experiment. The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose. SD reduced the number of cells positively stained with PCNA proliferation marker in mice skin. The study also showed that SD application without UVB exposure has no effect on the structure of skin. The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.

Show MeSH
Related in: MedlinePlus