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Assessment of Augmented Immune Surveillance and Tumor Cell Death by Cytoplasmic Stabilization of p53 as a Chemopreventive Strategy of 3 Promising Medicinal Herbs in Murine 2-Stage Skin Carcinogenesis.
- Source :
-
Integrative cancer therapies [Integr Cancer Ther] 2014 Jul; Vol. 13 (4), pp. 351-67. Date of Electronic Publication: 2013 Dec 19. - Publication Year :
- 2014
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Abstract
- Cancer is the final outcome of a plethora of events. Targeting the proliferation or inducing programmed cell death in a proliferating population is a major standpoint in the cancer therapy. However, proliferation is regulated by several cellular and immunologic processes. This study reports the inhibition of proliferation by augmenting immune surveillance, silencing acute inflammation, and inducing p53-mediated apoptosis of skin cancer by 3 promising medicinal extracts. We used the well-characterized model for experimental skin carcinogenesis in mice for 32 weeks to study the chemopreventive effect of the methanolic extracts of Trigonella foenumgraecum, Eclipta alba, and Calendula officinalis. All 3 extracts reduced the number, incidence, and multiplicity of tumors, which was confirmed by the pathologic studies that showed regressed tumors. There was a significant reduction in the PCNA+ nuclei in all treatment groups 32 weeks after the initiation. Mechanistic studies revealed that proliferative population in tumors is diminished by the restoration of the endogenous antioxidant defense, inhibition of the stress-related signal-transducing element NFκB, reduction of inflammation, enhancement of immunosurveillance of the genetically mutated cells, along with silencing of the cell cycle progression signals. Finally, all 3 medicinal extracts induced stable expression of p53 within the tumors, confirmed by the CFDA-Cy3 apoptosis assay. Results of our study confirm that these extracts not only limit the rate of proliferation by inhibition of the processes integral to cancer development but also induce stable cytoplasmic expression of p53-mediated apoptosis, leading to fewer and regressed tumors in mice.<br /> (© The Author(s) 2013.)
- Subjects :
- 9,10-Dimethyl-1,2-benzanthracene
Animals
Antioxidants metabolism
Apoptosis drug effects
Carcinogenesis drug effects
Cell Cycle Checkpoints drug effects
Cell Movement drug effects
Cell Proliferation drug effects
Chemoprevention methods
Female
Free Radicals metabolism
Immunologic Surveillance drug effects
Inflammation chemically induced
Inflammation metabolism
Inflammation prevention & control
Langerhans Cells drug effects
Mice
NF-kappa B antagonists & inhibitors
Proliferating Cell Nuclear Antigen analysis
Signal Transduction drug effects
Skin drug effects
Skin pathology
Skin Neoplasms chemically induced
Skin Neoplasms chemistry
Skin Neoplasms pathology
Tetradecanoylphorbol Acetate
Tumor Suppressor Protein p53 metabolism
Calendula
Eclipta
Phytotherapy
Plant Extracts therapeutic use
Skin Neoplasms prevention & control
Trigonella
Tumor Suppressor Protein p53 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1552-695X
- Volume :
- 13
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Integrative cancer therapies
- Publication Type :
- Academic Journal
- Accession number :
- 24363284
- Full Text :
- https://doi.org/10.1177/1534735413513831