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

Vipra Kundoor,Sherief Khalifa,Hesham Fahmy,Ajay Bommareddy,Chandradhar Dwivedi,Xiaoying Zhang

doi:10.3390/md504197

Vipra Kundoor, Sherief Khalifa + Show 4 more

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https://doi.org/10.3390/md504197

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Journal: Marine drugs	Publication Date: Dec 12, 2007
Citations: 36	License type: CC BY 4.0

Affiliation: Suez Canal University, South Dakota State University

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.

Highlights

Skin cancer is the most common of all cancer types, leading to the diagnosis of more than 1 million cases each year in the United States
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)
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 ultraviolet B (UVB)-induced carcinogenesis

Summary

Introduction

Skin cancer is the most common of all cancer types, leading to the diagnosis of more than 1 million cases each year in the United States. An estimated 10,850 deaths will occur in 2007 [1], resulting from repeated sunlight exposure in which ultraviolet B (UVB) radiation is a major environmental carcinogen that induces nonmelanoma skin cancer [2,3,4]. UVB radiation is absorbed by DNA which causes damage to the DNA, primarily at sites of adjacent pyrimidines in the form of dimers [3, 4, 6]. Mechanism(s) of the UVB-induced promotion are not been fully understood. Several factors such as generation of reactive oxygen species causing oxidative stress and activation of various signaling cascades including the synthesis of prostaglandins (PG) play a major role in clonal expansion of UVB-initiated cells into visible skin tumors [7,8,9]

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