Xiap Inhibitor and Antiestrogen Embelin Abrogates Metastasis and Augments Apoptosis in Estrogen Receptor Positive Human Breast Adenocarcinoma Cell Line MCF-7

Tamoxifen therapy for the treatment of hormone responsive breast cancer has limitations due to acquired resistance in the case of recurrences. Embelin, a known inhibitor of X-linked inhibitor of apoptosis protein (XIAP) was also reported to exhibit strong antiestrogenic effects in animal models. Dual role of embelin as a proapoptotic and antiestrogenic agent may have potential benefits in the therapy of breast cancer. In this study, the effects of embelin treatment on estrogen receptor positive Human breast adenocarcinoma (MCF-7) cells was investigated to primarily understand if embelin being an antiestrogen and XIAP inhibitor could be a potential alternative to tamoxifen therapy. Results revealed that, embelin at a concentration of 65 μg/ml attenuated proliferation, inhibited metastatic migration, modulated the expression of Bcl2, Caspases and induced apoptosis in MCF-7 cells which was found to be p53 mediated. Hence, chemotherapy with embelin could be a promising strategy to be experimented in hormone responsive breast cancers

Pro-Stimulatory Effects of Tinospora Cordifolia (Menispermaceae) on SAOS-2 Osteoblast Cells -Implications on Bone Remodeling and Therapy of Osteoporosis

ABSTRACT Osteoblasts, the bone forming cells are currently the most studied target for developing therapeutics to treat bone loss associated with various skeletal disorders including osteoporosis. Tinospora cordifolia (TC) is used in Ayurveda and other traditional medicinal systems to treat bone fractures. The aim of the present investigation is to evaluate the effects of aqueous and alcoholic extracts of TC on osteogenesis using a widely employed in vitro model system for human osteoblasts (human osteoblast like cells SAOS-2), thereby to explore the possibility of its usefulness to stimulate bone formation in osteoporotic conditions. Tests for cell viability and proliferation (crystal violet test, trypan blue dye exclusion test, MTT assay and NBT reduction test) were performed to study the effect of TC on the growth of osteoblasts. It was observed that ethanolic extract of TC stimulated proliferation of osteoblasts at a dosage of 25µg/ml (P<0.001) but, the aqueous extract of TC showed no influence on cell proliferation. The effect of alcoholic extract of TC on bone resorption was also studied on functional osteoclasts derived from RANKL activated murine macrophage like cells RAW 264.7. Results of the study implicated that ethanolic extract of TC extract elicits pro-stimulatory effects on osteoblasts, but is devoid of any such effects on osteoclast cells thereby indicating that it has no effect on bone resorption

Effects of Tinospora cordifolia (Menispermaceae) on the proliferation, osteogenic differentiation and mineralization of osteoblast model systems in vitro

Ethnopharmacological relevance: Ancient Indian ayurvedic literature prescribes Tinospora cordifolia as a remedy to rheumatoid arthritis, inflammatory and allied diseases of musculo skeletal system. Aim: To investigate the effects of the alcoholic extract of Tinospora cordifolia (TC) on the proliferation, differentiation and mineralization of bone like matrix on osteoblast model systems in vitro and hence its possible use as a potential anti-osteoporotic agent. Materials and methods: Two in vitro osteoblast model systems were used in the study viz., human osteoblast-like cells MG-63 and primary osteoblast cells isolated from femur of rats. Cell growth and viability was assessed by standard colorimetric assays like MTT assay. The cell differentiation into osteoblastic lineage was evaluated by the activities of bone marker alkaline phosphatase. The effect of the extract on matrix mineralization was assessed by alizarin red-s staining and Von kossa staining. Cell morphology was studied by phase contrast microscopy and light microscopy (Giemsa/crystal violet staining). Results: Results indicate that the alcoholic extract of TC at a dosage of 25 μg/ml stimulated the growth of osteoblasts, increased the differentiation of cells into osteoblastic lineage and increased the mineralization of bone like matrix on both the osteoblast model systems used in the study. Cell morphology studies clearly indicated the increase in cell numbers and absence of adverse change in the cell morphology on treatment with the extract. Conclusion: TC extract has a potential influence on osteogenesis and hence its use could be explored as a potential anti-osteoporotic agent. © 2012 Elsevier Ireland Ltd. All rights reserved

Ethnomedicine based evaluation of osteoprotective properties of Tinospora cordifolia on in vitro and in vivo model systems

Indian ethnomedicine acclaims the use of Tinospora cordifolia (TC) in the treatment of bone fractures and vat rakta (gout). The objective of the study is to investigate the effects of alcoholic extract of Tinospora cordifolia on bone remodeling (involving osteoblastic and osteoclastic actions) in vitro and protect against ovariectomy-induced bone loss in vivo. Human osteoblast-like cells MG-63 and primary osteoblast cells isolated from rat femur were used as osteoblast models and RAW macrophage cell line 264.7 induced to take up osteoclastic lineage using RANK ligand were used as osteoclast models in the current study. Sirius red staining, quantification of osteocalcin, cytopathological analysis by Hematoxylin/eosin staining and semiquantitative reverse transcription PCR (RT-PCR) was carried out to ascertain the effects of T. cordifolia extract on osteoblast cells. MTT assay was perfomed to understand the influence of T. cordifolia extract on osteoclast cells. Adult female Sprague-Dawley rats were used as in vivo models to study the effect of T. cordifolia on ovariectomy induced bone loss. Radiological (DEXA analysis), Biochemical (markers of bone formation and resorption), histopathological (Hematoxylin/eosin staining) and histomorphometric analysis of the bone was carried out. Treatment with T. cordifolia extract resulted in enhanced collagen deposition, increased levels of osteocalcin, increased expression of osteogenic genes all indicative of favourable osteoblastogenesis. Treatment with T. cordifolia extract did not exert any significant influence on the proliferation of osteoclasts. Pretreatment with T. cordifolia extract at a dose of 50 mg/kg body wt/day orally for 21 days followed by treatment for 12 weeks post ovariectomy was able to prevent ovariectomy-induced bone loss in vivo. Results of the study support the use of T. cordifolia in Indian ethnomedicine for the treatment of bone diseases and fractures. © 2016 Elsevier Masson SA