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Chemopreventive effects of sarcotriol on ultraviolet B-induced skin tumor development in SKH-1 hairless mice.

Kundoor V, Zhang X, Bommareddy A, Khalifa S, Fahmy H, Dwivedi C - Mar Drugs (2007)

Bottom Line: Tumor multiplicity was found 19.6, 5.2 in the control and ST treated groups respectively.Caspase-3, -8, -9 and p53 were significantly (P < 0.05) upregulated in ST treated group compared to Control group.Together, this study for the first time identifies the chemopreventive effects of ST in UVB-induced carcinogenesis possibly by inducing apoptosis and upregulating p53.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Box 2202C, Brookings, SD 57007, USA.

ABSTRACT
Sarcotriol (ST) has been shown to be chemopreventive on 7,12-dimethyl-benz(a)anthracene (DMBA) initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor development in CD-1 mice in recent studies from our laboratory. The objective of this study was to determine the chemopreventive effects of ST on ultraviolet B (UVB)-induced skin tumor development in female SKH-1 hairless mice, an experimental model relevant to human skin cancer development, and its possible mechanisms of action. Female SKH-1 mice were divided into two groups: Control and ST treated. Control was topically treated with 100 microliter acetone and ST treated group administered with 30 microgram ST in 100 microliter acetone one hour before UVB exposure. For UVB-induced tumorigenesis, carcinogenesis was initiated and promoted by UVB (180 mJ/cm(2)). Group weights and tumor counts were taken once every week. After 30 weeks, mice were sacrificed and dorsal skin samples were collected. The proteins from the skin sample were further used for SDS-PAGE and Western blotting using specific antibodies against caspase-3, caspase-8, caspase-9 and p53. Tumor multiplicity was found 19.6, 5.2 in the control and ST treated groups respectively. Caspase-3, -8, -9 and p53 were significantly (P < 0.05) upregulated in ST treated group compared to Control group. Together, this study for the first time identifies the chemopreventive effects of ST in UVB-induced carcinogenesis possibly by inducing apoptosis and upregulating p53.

No MeSH data available.


Related in: MedlinePlus

The skin cancer protective effect of sarcotriol: skin tumor incidence and multiplicity were significantly reduced in mice pretreated with sarcotriol (bottom) compared to the untreated control (top).
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f3-md504197: The skin cancer protective effect of sarcotriol: skin tumor incidence and multiplicity were significantly reduced in mice pretreated with sarcotriol (bottom) compared to the untreated control (top).

Mentions: The results of the present investigation revealed a delay in the onset of tumorigenesis in the animals pretreated with ST. In the Control group, the onset of tumors commenced at 12th week of promotion and reached 100% by the 20th week, whereas pretreatment with ST one hour before UVB, the onset of tumors were delayed until the 15th week of promotion and, moreover, it was only 75 % until the 23rd week. Tumor incidence was significantly (p < 0.05) lower in ST treated group than Control group until 28th weeks of promotion. By the end of the experiment, tumor incidence was found to be 100 and 92 % in the Control and ST treated group respectively. As shown in Figure 2b, ST treatment resulted in a significant (P < 0.05) reduction in the number of tumors per mouse compared to the Control group throughout the duration of experiment. The mean number of tumors at the end of experiment in Control and ST treated group was found to be 19.6 and 5.2 respectively. These results indicated that ST inhibited skin tumor development in both tumor incidence, to a lesser extent, and tumor multiplicity in the ST treated groups (Figure 3). There was no significant difference in the average mouse weight between the Control and ST treated group throughout the experiment (data not shown). Moreover, the skin of mice that were treated with ST appeared to be healthy and no toxic symptoms were observed.


Chemopreventive effects of sarcotriol on ultraviolet B-induced skin tumor development in SKH-1 hairless mice.

Kundoor V, Zhang X, Bommareddy A, Khalifa S, Fahmy H, Dwivedi C - Mar Drugs (2007)

The skin cancer protective effect of sarcotriol: skin tumor incidence and multiplicity were significantly reduced in mice pretreated with sarcotriol (bottom) compared to the untreated control (top).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2365695&req=5

f3-md504197: The skin cancer protective effect of sarcotriol: skin tumor incidence and multiplicity were significantly reduced in mice pretreated with sarcotriol (bottom) compared to the untreated control (top).
Mentions: The results of the present investigation revealed a delay in the onset of tumorigenesis in the animals pretreated with ST. In the Control group, the onset of tumors commenced at 12th week of promotion and reached 100% by the 20th week, whereas pretreatment with ST one hour before UVB, the onset of tumors were delayed until the 15th week of promotion and, moreover, it was only 75 % until the 23rd week. Tumor incidence was significantly (p < 0.05) lower in ST treated group than Control group until 28th weeks of promotion. By the end of the experiment, tumor incidence was found to be 100 and 92 % in the Control and ST treated group respectively. As shown in Figure 2b, ST treatment resulted in a significant (P < 0.05) reduction in the number of tumors per mouse compared to the Control group throughout the duration of experiment. The mean number of tumors at the end of experiment in Control and ST treated group was found to be 19.6 and 5.2 respectively. These results indicated that ST inhibited skin tumor development in both tumor incidence, to a lesser extent, and tumor multiplicity in the ST treated groups (Figure 3). There was no significant difference in the average mouse weight between the Control and ST treated group throughout the experiment (data not shown). Moreover, the skin of mice that were treated with ST appeared to be healthy and no toxic symptoms were observed.

Bottom Line: Tumor multiplicity was found 19.6, 5.2 in the control and ST treated groups respectively.Caspase-3, -8, -9 and p53 were significantly (P < 0.05) upregulated in ST treated group compared to Control group.Together, this study for the first time identifies the chemopreventive effects of ST in UVB-induced carcinogenesis possibly by inducing apoptosis and upregulating p53.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Box 2202C, Brookings, SD 57007, USA.

ABSTRACT
Sarcotriol (ST) has been shown to be chemopreventive on 7,12-dimethyl-benz(a)anthracene (DMBA) initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor development in CD-1 mice in recent studies from our laboratory. The objective of this study was to determine the chemopreventive effects of ST on ultraviolet B (UVB)-induced skin tumor development in female SKH-1 hairless mice, an experimental model relevant to human skin cancer development, and its possible mechanisms of action. Female SKH-1 mice were divided into two groups: Control and ST treated. Control was topically treated with 100 microliter acetone and ST treated group administered with 30 microgram ST in 100 microliter acetone one hour before UVB exposure. For UVB-induced tumorigenesis, carcinogenesis was initiated and promoted by UVB (180 mJ/cm(2)). Group weights and tumor counts were taken once every week. After 30 weeks, mice were sacrificed and dorsal skin samples were collected. The proteins from the skin sample were further used for SDS-PAGE and Western blotting using specific antibodies against caspase-3, caspase-8, caspase-9 and p53. Tumor multiplicity was found 19.6, 5.2 in the control and ST treated groups respectively. Caspase-3, -8, -9 and p53 were significantly (P < 0.05) upregulated in ST treated group compared to Control group. Together, this study for the first time identifies the chemopreventive effects of ST in UVB-induced carcinogenesis possibly by inducing apoptosis and upregulating p53.

No MeSH data available.


Related in: MedlinePlus