title: In vitro and in vivo evaluation of 2-chloroethylnitrosourea derivatives as antitumor agents.
abstract: OBJECTIVE
  To evaluate potential of Naphthal-NU, Napro-NU and 5-Nitro-naphthal-NU, 2-chloroethylnitrosourea compounds with substituted naphthalimide in the pre-clinical studies.
  
  
  METHODS
  In vitro cytotoxicity of three nitrosoureas was determined in human and mouse tumor cell lines by MTT assays. In vivo anti-tumor potential was evaluated in Sarcoma-180 (S-180) and Ehrlich's carcinoma (EC) solid tumors. Apoptosis in S-180 cells was analyzed by using Annexin V-Propidium Iodide (PI). Histological analysis of liver and kidney was performed at optimum dose (50 mg/kg). Expression status of CD4(+), CD8(+) and CD25(+) cells in treated mouse were also examined.
  
  
  RESULTS
  Significant tumor growth retardation by the compounds was noted in early and advanced disease groups, as the life span of drug treated mice increased considerably. Drug induced killing was observed by induction of apoptosis. Naphthal-NU and 5-Nitro-naphthal-NU were effective to normalize the tumor induced structural abnormalities of liver and kidney. The compounds have no immunotoxic effect on CD4(+) and CD8(+) T cells and down regulate CD4(+)CD25(+) regulatory T cells.
  
  
  CONCLUSIONS
  Overall data holds promise for the antitumor activity with lower toxicity of the compounds that can be utilized for the treatment of human malignant tumors.
authors: Department of Anticancer Drug Development, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors: A
authors: A
authors: Sen
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors: K K
authors: KK
authors: Goswami
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors: A
authors: A
authors: Mallick
authors: Pharmacology Division, Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001, India.
authors: A K
authors: AK
authors: Saxena
authors: Department of Anticancer Drug Development, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors: U
authors: U
authors: Sanyal
authors: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors: R
authors: R
authors: Baral
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D005038:Ethylnitrosourea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D053644:Naphthalimides / Q000737:chemistry* / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012510:Sarcoma 180 / Q000188:drug therapy / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D015704:CD4 Antigens; D016827:CD8 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D053644:Naphthalimides; C017139:1-(2-chloroethyl)-1-nitrosourea; D005038:Ethylnitrosourea