Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5846302 | Toxicology and Applied Pharmacology | 2014 | 12 Pages |
Abstract
Cigarette smoking is a crucial factor in the development and progression of multiple cancers including breast. Here, we report that repeated exposure to a fixed, low dose of cigarette smoke condensate (CSC) prepared from Indian cigarettes is capable of transforming normal breast epithelial cells, MCF-10A, and delineate the biochemical basis for cellular transformation. CSC transformed cells (MCF-10A-Tr) were capable of anchorage-independent growth, and their anchorage dependent growth and colony forming ability were higher compared to the non-transformed MCF-10A cells. Increased expression of biomarkers representative of oncogenic transformation (NRP-1, Nectin-4), and anti-apoptotic markers (PI3K, AKT, NFκB) were also noted in the MCF-10A-Tr cells. Short tandem repeat (STR) profiling of MCF-10A and MCF-10A-Tr cells revealed that transformed cells acquired allelic variation during transformation, and had become genetically distinct. MCF-10A-Tr cells formed solid tumors when implanted into the mammary fat pads of Balb/c mice. Data revealed that CSC contained approximately 1.011 μg Cd per cigarette equivalent, and Cd (0.0003 μg Cd/1 Ã 107 cells) was also detected in the lysates from MCF-10A cells treated with 25 μg/mL CSC. In similar manner to CSC, CdCl2 treatment in MCF-10A cells caused anchorage independent colony growth, higher expression of oncogenic proteins and increased PI3K-AKT-NFκB protein expression. An increase in the expression of PI3K-AKT-NFκB was also noted in the mice xenografts. Interestingly, it was noted that CSC and CdCl2 treatment in MCF-10A cells increased ROS. Collectively, results suggest that heavy metals present in cigarettes of Indian origin may substantially contribute to tumorigenesis by inducing intercellular ROS accumulation and increased expression of PI3K, AKT and NFκB proteins.
Keywords
CSCSCSCBenzo [a] pyreneMCF-10ADAPIDMBASTRAASFITCPBS4′, 6-diamidino-2-phenylindoleDMSOMTTROSHydrogen peroxideAAS, atomic absorption spectrometryShort tandem repeatTransformationdimethyl sulphoxidedihydroethidiumBreast cancerCigarette smoke condensatePhosphate buffered salineHeavy metalsfluorescein isothiocyanateH2O2DHEReactive oxygen species
Related Topics
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Environmental Science
Health, Toxicology and Mutagenesis
Authors
Purusottam Mohapatra, Ranjan Preet, Dipon Das, Shakti Ranjan Satapathy, Sumit Siddharth, Tathagata Choudhuri, Michael D. Wyatt, Chanakya Nath Kundu,