3, 3′-Diindolylmethane-encapsulated chitosan nanoparticles accelerate molecular events during chemical carcinogen-induced mammary cancer in Sprague Dawley rats
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.
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.
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.
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.
KeywordsMammary cancer DMBA DIM@CS-NP Caspase-9 Caspase-3
Dr. K. Pandiyan, Associate Professor, Department of Inorganic Chemistry, University of Madras, Guindy Campus, Chennai-600 025, Tamil Nadu, India for nanoparticles synthesis and characterization studies.
No funding source.
Compliance with ethical standards
Conflict of interest
The first author (S. Isabella) and the corresponding author (Dr. S. Mirunalini) declare that there are no conflicts of interest.
This study was approved by the Institutional Animal Ethics Committee (IAEC), regulated by the Committee for the Purpose of Control and Supervision of Experimental Animals (CPCSEA) (Reg No. 160/1999/CPCSEA and Proposal No. 1123).
This article does not contain any studies with human participants.
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