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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 effects of ST pretreatment on p53 on UVB-irradiated skin tumors of SKH-1 hairless mice. Values represent mean ± SE derived from at least three mice. Values of ST are percentages of control values quantitated by densitometry.
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f5-md504197: The effects of ST pretreatment on p53 on UVB-irradiated skin tumors of SKH-1 hairless mice. Values represent mean ± SE derived from at least three mice. Values of ST are percentages of control values quantitated by densitometry.

Mentions: Based on the hypothesis that ST induces apoptosis by upregulating the caspase levels as its possible mechanism of chemoprevention against skin tumor development in CD-1 mice [16], the effects of ST on caspase-3 were analyzed. As shown in Figure 4, ST significantly (P < 0.05) upregulated the levels of caspase-3. We observed that the value of caspase-3 as compared in ST treated group was found to be 4.9 fold higher than Control group. In order to assess the mechanism of caspase-3 activation, a further study was carried out to find out whether caspase-9 and -8 are activated as upstream effectors leading to caspase-3 activation. We observed a significant (P < 0.05) increase in caspase-9 and -8 activities as shown in Figure 5. The levels of caspase-8 in ST treated group were found to be 5.7 fold higher than Control. Whereas the values of caspase-9 in ST treated group were 3.9 fold higher than Control. These results suggest that ST induced apoptotic cell death might be mediated by both extrinsic and intrinsic pathways of apoptosis in tumor cells in UVB-induced carcinogenesis.


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 effects of ST pretreatment on p53 on UVB-irradiated skin tumors of SKH-1 hairless mice. Values represent mean ± SE derived from at least three mice. Values of ST are percentages of control values quantitated by densitometry.
© Copyright Policy
Related In: Results  -  Collection

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

f5-md504197: The effects of ST pretreatment on p53 on UVB-irradiated skin tumors of SKH-1 hairless mice. Values represent mean ± SE derived from at least three mice. Values of ST are percentages of control values quantitated by densitometry.
Mentions: Based on the hypothesis that ST induces apoptosis by upregulating the caspase levels as its possible mechanism of chemoprevention against skin tumor development in CD-1 mice [16], the effects of ST on caspase-3 were analyzed. As shown in Figure 4, ST significantly (P < 0.05) upregulated the levels of caspase-3. We observed that the value of caspase-3 as compared in ST treated group was found to be 4.9 fold higher than Control group. In order to assess the mechanism of caspase-3 activation, a further study was carried out to find out whether caspase-9 and -8 are activated as upstream effectors leading to caspase-3 activation. We observed a significant (P < 0.05) increase in caspase-9 and -8 activities as shown in Figure 5. The levels of caspase-8 in ST treated group were found to be 5.7 fold higher than Control. Whereas the values of caspase-9 in ST treated group were 3.9 fold higher than Control. These results suggest that ST induced apoptotic cell death might be mediated by both extrinsic and intrinsic pathways of apoptosis in tumor cells in UVB-induced carcinogenesis.

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