3, 3'-Diindolylmethane-encapsulated chitosan nanoparticles accelerate molecular events during chemical carcinogen-induced mammary cancer in Sprague Dawley rats.

Affiliation

Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu, 608 002, India. [Email]

Abstract

BACKGROUND : 3, 3'-Diindolylmethane (DIM) is a dietary indole compound; its medical application was limited because of poor bioavailability, unsatisfying dispersity, and rapid metabolism. To conquer this problem, nanoformulation of DIM was synthesized and investigated its mechanism-based chemotherapeutic potential.
METHODS : 7,12-Dimethylbenz(a)anthracene (DMBA) 25 mg/kg b.wt initiated mammary carcinogenesis in rats, the investigational tumor model that closely resembles human mammary cancer. Rats had accessed after 8 weeks of tumor formation, DIM 10 mg/kg b.wt. and DIM@CS-NP 0.5 mg/kg b.wt. were administrated orally for 8 weeks.
RESULTS : The treatment with DIM@CS-NP 0.5 mg/kg b.wt. on DMBA-induced tumor-bearing rats was down-regulated Cyclin D1, Bcl-2 expression, and up-regulated proapoptotic proteins such as Bax, p53, Cytochrome-C, Caspase-9, and Caspase-3 as compared to DIM 10 mg/kg b.wt. In addition, the mRNA expressions of Cyclin D1, Bcl-2 decreased and increased Bax, p53 expression, in immunohistochemical analysis decreased expressions of Cyclin D1 and PCNA in the treatment of DIM@CS-NP 0.5 mg/kg b.wt. compared to DIM 10 mg/kg b.wt. Histological analysis of tumor tissues shows abnormal in collagen deposition in with Masson's trichrome (MT) and Picrosirius red (PR) staining, the treatment of DIM@CS-NP 0.5 mg/kg b.wt. reduced the collagen deposition as compared to DIM 10 mg/kg b.wt.
CONCLUSIONS : Our results clearly provide evidence that DIM@CS-NP exerts chemotherapeutic effect than DIM in DMBA model of mammary cancer by hold back anomalous tumor cell proliferation and inducing apoptosis to intervene through alterations of up-regulated and down-regulated molecules. Taken together, the data provide new evidence for mechanism action of DIM@CS-NP on mammary cancer.

Keywords

Caspase-3,Caspase-9,DIM@CS-NP,DMBA,Mammary cancer,

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