| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Epidemiology and Prevention |
1 Department of Pharmaceutical Sciences, School of Pharmacy, and 2 University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado
Here, we assessed the protective effect of silibinin on UVB-induced skin carcinogenesis in SKH-1 hairless mice. Topical application of silibinin before or immediately after UVB exposure or its dietary feeding resulted in a strong protection against photocarcinogenesis, in terms of tumor multiplicity (60–66%; P < 0.001), tumor volume per mouse (93–97%; P < 0.001) and tumor volume per tumor (80–91%; P < 0.001). Silibinin also moderately inhibited tumor incidence (5–15%; P < 0.01) and delayed tumor latency period (up to 4 weeks; P < 0.01–0.001). To investigate in vivo molecular mechanisms of silibinin efficacy, tumors and uninvolved skin from tumor-bearing mice were examined immunohistochemically for proliferation, p53, apoptosis, and activated caspase-3. Silibinin treatment showed a strong decrease (P < 0.001) in proliferating cell nuclear antigen-positive cells and an increase in p53-positive (P < 0.005–0.001), terminal deoxynucleotidyltransferase-mediated nick end labeling-positive (P < 0.005–0.001), and cleaved caspase-3–positive cells (P < 0.001). Western blot analysis of normal skin and tumor lysates showed that silibinin decreases the levels of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 and associated cyclins A, E, and D1, together with an up-regulation of Cip1/p21, Kip1/p27, and p53. Silibinin also showed a strong phosphorylation of extracellular signal-regulated protein kinase 1/2, stress-activated protein kinase/c-JUN NH2-terminal kinase 1/2, and p38 mitogen-activated protein kinases but inhibited Akt phosphorylation and decreased survivin levels with an increase in cleaved caspase-3. Together, these results show a strong preventive efficacy of silibinin against photocarcinogenesis, which involves the inhibition of DNA synthesis, cell proliferation, and cell cycle progression and an induction of apoptosis. Furthermore, these results also identify in vivo molecular mechanisms of silibinin efficacy against photocarcinogenesis.
This article has been cited by other articles:
|
|
 |
|
  C.-J. Lin, R. Sukarieh, and J. Pelletier Silibinin inhibits translation initiation: implications for anticancer therapy Mol. Cancer Ther., June 1, 2009; 8(6): 1606 - 1612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Singh, K. Raina, G. Deep, D. Chan, and R. Agarwal Silibinin Suppresses Growth of Human Prostate Carcinoma PC-3 Orthotopic Xenograft via Activation of Extracellular Signal-Regulated Kinase 1/2 and Inhibition of Signal Transducers and Activators of Transcription Signaling Clin. Cancer Res., January 15, 2009; 15(2): 613 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Jung, K. W. Lee, S. Byun, N. J. Kang, S. H. Lim, Y.-S. Heo, A. M. Bode, G. T. Bowden, H. J. Lee, and Z. Dong Myricetin Suppresses UVB-Induced Skin Cancer by Targeting Fyn Cancer Res., July 15, 2008; 68(14): 6021 - 6029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Singh, G. Deep, M.-J. Blouin, M. N. Pollak, and R. Agarwal Silibinin suppresses in vivo growth of human prostate carcinoma PC-3 tumor xenograft Carcinogenesis, December 1, 2007; 28(12): 2567 - 2574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Roy, M. Kaur, C. Agarwal, M. Tecklenburg, R. A. Sclafani, and R. Agarwal p21 and p27 induction by silibinin is essential for its cell cycle arrest effect in prostate carcinoma cells Mol. Cancer Ther., October 1, 2007; 6(10): 2696 - 2707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Crowell, V. E. Steele, and J. R. Fay Targeting the AKT protein kinase for cancer chemoprevention Mol. Cancer Ther., August 1, 2007; 6(8): 2139 - 2148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Comelli, U. Mengs, C. Schneider, and M. Prosdocimi Toward the Definition of the Mechanism of Action of Silymarin: Activities Related to Cellular Protection From Toxic Damage Induced by Chemotherapy Integr Cancer Ther, June 1, 2007; 6(2): 120 - 129. [Abstract] [PDF]
|
|
|
|
|
|
G. Deep and R. Agarwal Chemopreventive Efficacy of Silymarin in Skin and Prostate Cancer Integr Cancer Ther, June 1, 2007; 6(2): 130 - 145. [Abstract] [PDF]
|
|
|
|
|
|
M. Gu, R. P. Singh, S. Dhanalakshmi, C. Agarwal, and R. Agarwal Silibinin Inhibits Inflammatory and Angiogenic Attributes in Photocarcinogenesis in SKH-1 Hairless Mice Cancer Res., April 1, 2007; 67(7): 3483 - 3491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P Singh and R. Agarwal Mechanisms of action of novel agents for prostate cancer chemoprevention. Endocr. Relat. Cancer, September 1, 2006; 13(3): 751 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dwivedi, H. B. Valluri, X. Guan, and R. Agarwal Chemopreventive effects of {alpha}-santalol on ultraviolet B radiation-induced skin tumor development in SKH-1 hairless mice Carcinogenesis, September 1, 2006; 27(9): 1917 - 1922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gu, R. P. Singh, S. Dhanalakshmi, S. Mohan, and R. Agarwal Differential effect of silibinin on E2F transcription factors and associated biological events in chronically UVB-exposed skin versus tumors in SKH-1 hairless mice. Mol. Cancer Ther., August 1, 2006; 5(8): 2121 - 2129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Meeran, S. Katiyar, C. A. Elmets, and S. K. Katiyar Silymarin inhibits UV radiation-induced immunosuppression through augmentation of interleukin-12 in mice. Mol. Cancer Ther., July 1, 2006; 5(7): 1660 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Singh, G. Deep, M. Chittezhath, M. Kaur, L. D. Dwyer-Nield, A. M. Malkinson, and R. Agarwal Effect of silibinin on the growth and progression of primary lung tumors in mice. J Natl Cancer Inst, June 21, 2006; 98(12): 846 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Singh, S. Dhanalakshmi, S. Mohan, C. Agarwal, and R. Agarwal Silibinin inhibits UVB- and epidermal growth factor-induced mitogenic and cell survival signaling involving activator protein-1 and nuclear factor-{kappa}B in mouse epidermal JB6 cells Mol. Cancer Ther., May 1, 2006; 5(5): 1145 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-N. Chen, Y.-S. Hsieh, C.-L. Chiang, H.-L. Chiou, S.-F. Yang, and S.-C. Chu Silibinin Inhibits Invasion of Oral Cancer Cells by Suppressing the MAPK Pathway Journal of Dental Research, March 1, 2006; 85(3): 220 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Varghese, C. Agarwal, A. Tyagi, R. P. Singh, and R. Agarwal Silibinin Efficacy against Human Hepatocellular Carcinoma Clin. Cancer Res., December 1, 2005; 11(23): 8441 - 8448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ruiz, M. Santos, M. F. Lara, C. Segrelles, C. Ballestin, and J. M. Paramio Unexpected Roles for pRb in Mouse Skin Carcinogenesis Cancer Res., November 1, 2005; 65(21): 9678 - 9686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gu, S. Dhanalakshmi, S. Mohan, R. P. Singh, and R. Agarwal Silibinin inhibits ultraviolet B radiation-induced mitogenic and survival signaling, and associated biological responses in SKH-1 mouse skin Carcinogenesis, August 1, 2005; 26(8): 1404 - 1413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dhanalakshmi, C. Agarwal, R. P. Singh, and R. Agarwal Silibinin Up-regulates DNA-Protein Kinase-dependent p53 Activation to Enhance UVB-induced Apoptosis in Mouse Epithelial JB6 Cells J. Biol. Chem., May 27, 2005; 280(21): 20375 - 20383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gu, S. Dhanalakshmi, R. P. Singh, and R. Agarwal Dietary Feeding of Silibinin Prevents Early Biomarkers of UVB Radiation-Induced Carcinogenesis in SKH-1 Hairless Mouse Epidermis Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1344 - 1349. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
