Diindolylmethane and Lupeol Modulates Apoptosis and Cell Proliferation in N-Butyl-N-(4-Hydroxybutyl) Nitrosamine Initiated and Dimethylarsinic Acid Promoted rat Bladder Carcinogenesis.
Bladder cancer has been shown to resist programmed cell death with altered expression of both pro-apoptotic and anti-apoptotic proteins. To study is to investigate the apoptotic properties of Diindolylmethane (DIM) and Lupeol on N-Butyl-N-(4-hydroxybutyl) Nitrosamine (BBN) initiated and Dimethylarsinic Acid (DMA) promoted urinary bladder cancer. Sixty male Wistar rats were divided into 6 groups. Group I: Control. Group II: Rats were experimentally developed bladder carcinogenesis with BBN and DMA. Group III and IV: DIM and lupeol were administered after BBN treatment for 28 weeks. Group V and VI: DIM and lupeol alone treatment for 36 weeks. All the experimental rats were maintained and euthanized after 36 weeks protocol. Urinary bladder tissues were collected and processed for further investigations. Apoptotis and cell proliferative marker such as Bax, Bcl-2, caspase-3, caspase-9 and PCNA were quantified using immunohistochemical analysis. The Immunohistochemical expression of Bax, Bcl-2, caspase-3, caspase-9 and PCNA were aberrant in BBN + DMA treated tumor group. Administration of DIM and lupeol inhibited the progression of bladder cancer, induced the expression of apoptotic Bax, caspase-3, caspase-9 and inhibited the expression of anti-apoptotic Bcl-2, PCNA in the urinary bladder of rats. Administration of diindolylmethane and lupeol treatment induces apoptosis and cellular proliferation by its anti-carcinogenic properties. From our results DIM and lupeol would be the agent or adjunct for the treatment of bladder carcinogenesis.
Department of Medical Research, SRM Medical College Hospital Research Centre, SRM University, Kattankulathur, 603203, Kanchipuram District, Tamilnadu, India.
Bhoopathy
B
Prabhu
Department of Medical Research, SRM Medical College Hospital Research Centre, SRM University, Kattankulathur, 603203, Kanchipuram District, Tamilnadu, India.
Annamalai
A
Sivakumar
Department of Medical Research, SRM Medical College Hospital Research Centre, SRM University, Kattankulathur, 603203, Kanchipuram District, Tamilnadu, India. drssundaresan@hotmail.com.
Sivapatham
S
Sundaresan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002085:Butylhydroxybutylnitrosamine / Q000009:adverse effects*; D002101:Cacodylic Acid / Q000009:adverse effects*; D063646:Carcinogenesis; D002273:Carcinogens / Q000008:administration & dosage; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000094042:Lupanes
D002085:Butylhydroxybutylnitrosamine; D002101:Cacodylic Acid; D002273:Carcinogens; D053148:Caspase 3; D053453:Caspase 9; D007211:Indoles; D053978:Pentacyclic Triterpenes; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C010480:lupeol; D000094042:Lupanes; C016392:3,3'-diindolylmethane
Apoptosis; Cell proliferation; Diindolylmethane; Lupeol and bladder cancer