title: 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.
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.
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Farrah
authors.initials: F
authors.lastname: Ali
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Rehan
authors.initials: R
authors.lastname: Khan
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Abdul Quaiyoom
authors.initials: AQ
authors.lastname: Khan
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Md Abdul
authors.initials: MA
authors.lastname: Lateef
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Tahir
authors.initials: T
authors.lastname: Maqbool
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India sarwat786@rediffmail.com.
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D020838:Calendula; D063646:Carcinogenesis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention / Q000379:methods; D036601:Eclipta; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D007157:Immunologic Surveillance / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D007801:Langerhans Cells / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000737:chemistry / Q000473:pathology / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate; D029910:Trigonella; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D016328:NF-kappa B; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate
keywords: antiproliferative; immunosurveillance; medicinal herbs; p53; skin cancer