In Vivo Assessment of Anti-Tumor Activity of Methyl ۲'-Methyl-۱,۳-dioxo-۱,۱',۲',۳,۵',۶',۷',۷a'-octahydrospiro[indene-۲,۳'-pyrrolizidine]-۲' carboxylate (۶) on ۷,۱۲ dimethylbenz(a) Anthracene-Induced Mammary Tumors in Rat

Objective- Breast cancer is one of the most serious problems in oncology. Alkaloids pyrrolizidine are widely found in nature and exhibited versatile biological activities. The aim of the present study was to assess anti-tumor activity of methyl ۱,۳-dioxo-۱,۱',۲',۳,۵',۶',۷',۷a'-octahydrospiro[indene-۲,۳'-pyrrolizidine]-۲'-carboxylate (۶) on ۷,۱۲ dimethylbenz(a) anthracene (DMBA)-induced mammary tumors in rat. Design- Experimental study.Animals- Twenty-one female Wistar atsProcedures- ۷-Week-old female Wistar rats (۱۸۰ g body weight) were randomized into three groups of seven animals each. DMBA-induced mammary tumors was achived using DMBA dissolved in ۱ml of vehicle (۰.۵ ml of DMSO plus ۰.۵ ml of saline) and injected by subcutaneous injection beneath the mammary gland on either side. Tumor yield and size were stabilized after ۹۰ days with the initiation of DMBA. Healthy intact animals (NC) were considered as a normal control feeding on pellets and tap water. In group DMBA, the tumor was induced by DMBA. In group DMBA/۷d the animals with tumor received ۱۰۰ µL ۶ dissolved in DMSO (۰.۲۵ µM) solution intraperitoneally for one week. Synthesis of ۶ was accomplished and the structure of new product was assigned by their ۱H/۱۳C NMR, IR, CH-COSY and mass spectral data as well as the elemental analysis. Results- The overall tumor analysis showed that ۶ treatment significantly inhibited the breast tumor incidence, tumor multiplicity, and tumor size in the DMBA-initiated rat model. ۶ treatment significantly inhibited the total volume of tumors per rat. Conclusion and Clinical Relevance-The findings of the present study showed that the ۶ treatment was significantly effective in reduction of tumors versus the cancer controls.

Keywords:

Breast carcinogenesis , ۷-۱۲-Dimethylbenz(a)anthracene , Indene-۲-۳'-pyrrolizidine , mammary tumors