ABSTRACT
Breast cancer is a major public health problem and the low effectiveness of conventional therapies to achieve long-term survival results in increased mortality associated with advanced breast cancers. Betulinic acid (BA) is a pentacyclic triterpene which can be isolated from number of plants grown in the tropics. It exhibits cytotoxic activity against variety of cancer cell lines. In the present study, the in vitro cytotoxic activity and in vivo antitumor activity of BA was evaluated in athymic nude mice bearing MCF-7 breast adenocarcinoma xenografts. In vitro cytotoxic activity of BA on MCF-7 cells was studied using the MTT assay and BA was cytotoxic towards MCF-7 cells with IC50 value of 13.5 microg/mL. The antitumor activity of BA was studied at concentrations of 50 and 100 mg/kg body weight in mice injected with MCF-7 cells. BA treatment delayed tumor formation and statistically significant reduction (P < 0.0001) of 52 and 77% in the tumor size at concentrations of 50 and 100 mg, respectively was observed. Histopathological analysis of tumors revealed decreased angiogenesis, proliferation and invasion in BA treated animals. This is one of the first studies demonstrating the in vivo antitumor activity of BA on MCF-7 breast cancer tumors in nude mice. The antitumor effect of BA can further be enhanced by use of combination therapy and novel drug delivery systems, thus making it a promising candidate for management of breast cancer patients.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Neovascularization, Pathologic , Triterpenes/pharmacology , Animals , Breast Neoplasms/blood supply , Breast Neoplasms/drug therapy , Female , Humans , Immunoenzyme Techniques , Mice , Mice, Inbred BALB C , Mice, Nude , Pentacyclic Triterpenes , Tumor Cells, Cultured , Betulinic AcidABSTRACT
Breast cancer is a common malignancy in women all over the world and novel therapeutic approaches are required for the treatment of patients who become refractory to conventional therapies. Thyroid cancer is being treated successfully with radioiodine since many years. The iodide is transported inside the thyroid epithelial cell via sodium iodide symporter (NIS) which is a trans-membrane protein. The present study was aimed to explore the uptake of radioiodide (RAI) and the expression of NIS in breast tissues of invasive ductal carcinoma patients. Breast tissues from tumor region (Tu-Br) as well as corresponding normal region (N-Br) were collected from patients of invasive ductal carcinoma. In vitro RAI uptake, its efflux and NIS expression were studied. The uptake of RAI (1.98+/-1.75 x 10(5) cpm/g) in Tu-Br was significantly higher as compared to that observed in N-Br (0.31+/-0.27 x 10(5) cpm/g) and fast efflux was observed in the tissue samples. NIS gene expression was positive in 41.66% (10/24) samples of Tu-Br. None of the N-Br samples expressed NIS gene. In 14 samples of Tu-Br, RAI uptake as well as NIS expression was studied. In 50% of these Tu-Br samples RAI uptake as well as of NIS gene expression was positive. The results indicate that RAI uptake is significantly higher in breast tumor tissues as compared to their normal counterpart and in future radioiodine may be an important agent for treatment of breast cancer.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/radiotherapy , Iodine Radioisotopes/therapeutic use , Symporters/genetics , Adult , Aged , Base Sequence , Breast Neoplasms/metabolism , Female , Gene Expression , Humans , Iodine Radioisotopes/pharmacokinetics , Middle Aged , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolismABSTRACT
Monoclonal antibodies to human thyroglobulin were produced using the hybridoma technique. Two monoclonal antibodies D5I and F9I were radiolabeled with 125I and used for radioimmunolocalization studies in an immunosuppressed animal model bearing xenografts of human thyroid tumor tissue. Biodistribution studies were carried out at various time intervals post-injection. Maximum tumor uptake was obtained at 72 hr after administration of the antibodies. The absolute tumor uptake (ATU) expressed as percentage of injected dose per gram of tissue (% ID/g) was 15.49 +/- 2.47, 4.51 +/- 0.69 and 2.50 +/- 0.41 for D5I, F9I and control Igs respectively. The tumor to blood ratios (T/B) obtained were 3.01 +/- 0.43 for D5I, 0.98+/-0.2 for F9I and 0.47 +/- 0.12 for control Igs. ATU as well as T/B ratio obtained with D5I was significantly higher as compared to F9I and control Igs. The results indicated the potential application of radiolabeled monoclonal antibodies to human thyroglobulin for tumor targetting in patients of differentiated thyroid carcinoma, particularly those metastases which did not concentrate radioiodine.
