Colloidal Vesicular System of Inositol Hexaphosphate to Counteract DMBA Induced Dysregulation of Markers Pertaining to Cellular Proliferation/Differentiation and Inflammation of Epidermal Layer in Mouse Model
Authors: Poonam Parashar
Prakash Tiwari
Narayan P Yadav
Krishna P Gupta
Shubhini A Saraf
Chandra Bhushan Tripathi
Malti Arya
Mahendra Singh
Gaurav Kaithwas
Priyam Sinha
Journal: Molecular Pharmaceutics (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: RT-PCR; SK-MEL-2 cell line; Western blotting; histopathology; niosomes
Affiliations: Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University , Vidya Vihar, Raebareli Road, Lucknow-226025, U.P., India., Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research , Post Box No. 80, Mahatma Gandhi Marg, Lucknow-226001, U.P., India., CSIR-Central Institute of Medicinal and Aromatic Plants , PO CIMAP, Lucknow-226015, U. P., India.

Abstract:  Cancer is a global health problem and chemoprevention is a promising approach for reducing cancer burden. Inositol hexaphosphate (IP6), a natural bioactive constituent of cereals, legumes, etc., has momentous potential as an antiangiogenic agent, that specifically affects malignant cells. The shortcoming is its quick absorption on oral/topical administration. Niosomes are flexible carriers for topical drug delivery. The central venture of current research was to optimize and characterize niosomal delivery system of IP6 for treatment of skin cancer. Thin film hydration method was utilized to prepare IP6 niosomes, and these were dispersed as a suspension in a suitable base. Developed formulations were analyzed for various physicochemical and pharmacological parameters such as particle size, encapsulation efficiency, morphology, drug release, texture analysis, irritability, cell line studies, Western blotting, RT-PCR, and histopathology. IP6 niosomal suspension and IP6 in acetone displayed IC50 value at the concentration of 0.96 mM (0.63 mg/mL) and 1.39 mM (0.92 mg/mL), respectively. IP6 niosomal suspension showed significantly higher (p &lt; 0.05) activity and showed cytotoxic effect in SK-MEL-2 cancer cell line. Crucial events of cellular proliferation and differentiation, like expression of ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), cycloxygenase-2 (COX-2) and Cyclin D1 were initiated from the fourth hour through application of 7,12-dimethylbenzanthracene (DMBA) on albino mice. The DMBA altered expression of aforesaid enzymes was significantly (P &lt; 0.001) prevented by concomitant application of niosomal formulations. Results of cell line study, Western blotting, RT-PCR, and histopathology suggested that IP6 niosomal suspension could constitute a promising approach for prevention of cellular proliferation as well as DMBA induced dysregulation of cellular proliferation/differentiation and inflammation. 

Retracted: No

PubPeer comments:
 In this article, Yang and colleagues explore the issue of CD161+CD4+ T cells during primary exposure to *Mycobacterium tuberculosis* (Mtb). CD161+CD4+ T cells secreted significantly more cytokines that CD161-CD4+ T cells that may be important during immune response to primary Mtb infection. However, the authors did not mention the fact, that CD161+ CD4+ T cells are largely memory T cells while CD161-CD4+ T cells are known to be consisted of memory T cells and naive T cells. As naive T cells usually secrete less cytokines that memory T cells, the difference in levels of cytokine secretion between CD161+CD4+ and CD161-CD4+ T cells might be explained by that fact (Takahashi et al., 2006). The authors speculated, that CD161-LLT1 receptor-ligand interaction may be implicated in the inhibition of Mtb growth. CD161 ligation by anti-CD161 antibodies abrogated the ability of CD161+CD4+ T cells to inhibit Mtb growth in infected cells, but the LLT1 expression (CD161 ligand) was not evaluated in the utilised cell lines. Finally, the Yang and colleagues indicated, that CD161+CD4+ T cells may be involved in killing Mtb without prior antigen presentation and that CD161 pathway could be directly involved in this process. However, CD161 is known to act only in TCR-dependent manner as ligation of CD161 by anti-CD161 antibodies in TCR-independent manner had no effect on cellular response (Fergusson et al., 2014). Minor problem with the article is that the authors claimed to utilise anti-CD161 antibody HP3G8 for flow cytometry analysis. I think that authors meant anti-CD161 HP3G10 which is the clone often used in the research focused on CD161. References: Takahashi et al., 2006. *J Immunol*. Expression of CD161 (NKR-P1A) defines subsets of human CD4 and CD8 T Cells with different functional activities. Fergusson et al., 2014. *Front Immunol*. CD161 defines a transcriptional and functional phenotype across distinct human T Cell lineages. ,