Preventive effects of butyric acid, nicotinamide, calcium glucarate alone or in combination during the 7, 12-dimethylbenz (a) anthracene induced mouse skin tumorigenesis via modulation of K-Ras-PI3K-AKTpathway and associated micro RNAs
Authors: Syed S Y H Qadri
Krishna P Gupta
Prakash Tiwari
Manuraj Pandey
Satya Sahay
Journal: Biochimie (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Chemoprevention; Combination; Natural agents; PI3K/AKT; Skin tumors
Affiliations: Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, 226001, India; PhD Programme, Academy of Scientific and Innovative Research (AcSIR), India., Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, 226001, India., Pathology Division, National Institute of Nutrition, Hyderabad, India., Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, 226001, India. Electronic address: .

Abstract:  Skin cancer is among the most common cancers worldwide and identifiable molecular changes for early and late stage of skin tumorigenesis can suggest the better targets for its control. In this study, we investigated the status of K-Ras-PI3K-AKTpathway followed by NF-κB, cyclin D1, MMP-9 and regulatory micro RNA during 7, 12-dimethylbenz[a]anthracene (DMBA) induced mouse skin tumorigenesis and its prevention by butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG), individually or in combination with respect to time. DMBA upregulated the K-Ras, PI3K, Akt, NF-κB, cyclin D1 and MMP-9, but downregulated the PTEN in a time dependent manner. DMBA also reduced the levels of micoRNA let-7a but induced the levels of miR-21 and miR-20a as a function of time. BA, NA and CAG were found to prevent DMBA induced changes, but they were most effective when used together in a combination. Reduced let-7a and miR-211 were correlated with the overexpression of K-Ras and MMP-9. Overexpression of miR-21 and miR-20a was correlated with the down regulation of PTEN and overexpression of Cyclin D1. Collectively, the enhanced chemopreventive potential of natural compound in combination via regulation of K-Ras-PI3K-AKTpathway along with regulatory micro RNAs provide a newer and effective mean for cancer management. 

Retracted: No

PubPeer comments:
 Very similar blots. Top:Inverted image from Figure 2 II. Bottom: Original image from Figure 2 II. *** ![file] *** ![file] , 
 #1 The 8-week and 32-week panels remind me of a Multiple Birth convention, when all the identical triplets line up for a photograph. So separate blots of PI3K were made for samples of 1-week, 8-week and 32-week treatment? Then normalised with a single actin blot? How does that work? , 
 Dear Sir, Thank you for your review of papers. Is it possible to review papers before submission to journals? It will help to write good quality papers. Actually in this study, status of K-Ras-PI3K-AKT pathway and regulatory micro RNA were investigated during DMBA induced mouse skin tumorigenesis and its prevention by natural agents incombination with respect to time. Three samples from each group were used for expression analysis by WB and PCR and were subjected to statistical analysis (n =3). All values were normalized by individual B actin for each time point. However, only one panel of B actin was shown in figures as representative of the loading control. For expression analysis of each gene separate PCR and WB was performed (Including PI3K gene PCR and WB). For your kind perusal please find attached herewith images of PI3K PCR gel and WB. Thanking You. ![file] ![file] ![file] ,