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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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Structure of sarcophine-diol (SD).
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marinedrugs-10-02111-f001: Structure of sarcophine-diol (SD).

Mentions: Epidemiological data suggest that sunscreens alone are not sufficient for preventing skin cancer due to the need of frequent reapplication and the variability among commercially available sunscreens. Thus, there is a need for more effective ways to prevent skin cancer [9,10]. Recently, marine organism compounds have gained attention for their potential as chemopreventive agents due to their considerable biodiversity [11,12,13]. One of those marine compounds is sarcophine which is extracted from the soft coral Sarcophyton glaucum. One of the semisynthetic derivatives of sarcophine is sarcophine-diol (SD, Figure 1) [14,15,16]. Our laboratory has reported its chemopreventive effects against chemically-induced skin carcinogenesis in CD-1 mice [17]. Also, SD at 30 μg/dose in a UVB (180 mJ/cm2) induced skin carcinogenesis in a SKH-1 hairless mice model significantly inhibited tumor multiplicity and tumor area, without signs of toxicity in the animals. In the same experiment, SD increased the activation of cleaved caspases 3 and 8 in mice skin tissue [18]. Mechanistic studies performed in our laboratory showed that SD decreased cell viability and cell proliferation of the A431 squamous carcinoma cell line in a dose and time-dependent manner and caused apoptosis and DNA fragmentation [19]. Recent reports showed that SD has antineoplastic effects in vitro in the mouse melanoma cell line B16F10[20].


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)

Structure of sarcophine-diol (SD).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

marinedrugs-10-02111-f001: Structure of sarcophine-diol (SD).
Mentions: Epidemiological data suggest that sunscreens alone are not sufficient for preventing skin cancer due to the need of frequent reapplication and the variability among commercially available sunscreens. Thus, there is a need for more effective ways to prevent skin cancer [9,10]. Recently, marine organism compounds have gained attention for their potential as chemopreventive agents due to their considerable biodiversity [11,12,13]. One of those marine compounds is sarcophine which is extracted from the soft coral Sarcophyton glaucum. One of the semisynthetic derivatives of sarcophine is sarcophine-diol (SD, Figure 1) [14,15,16]. Our laboratory has reported its chemopreventive effects against chemically-induced skin carcinogenesis in CD-1 mice [17]. Also, SD at 30 μg/dose in a UVB (180 mJ/cm2) induced skin carcinogenesis in a SKH-1 hairless mice model significantly inhibited tumor multiplicity and tumor area, without signs of toxicity in the animals. In the same experiment, SD increased the activation of cleaved caspases 3 and 8 in mice skin tissue [18]. Mechanistic studies performed in our laboratory showed that SD decreased cell viability and cell proliferation of the A431 squamous carcinoma cell line in a dose and time-dependent manner and caused apoptosis and DNA fragmentation [19]. Recent reports showed that SD has antineoplastic effects in vitro in the mouse melanoma cell line B16F10[20].

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