Antiproliferative effects of total alkaloid extract of roots of Chassalia curviflora (Wall.) Thwaites on cancer cell lines

389-395Chassalia curviflora is used in folklore medicines for treating several ailments and infections owing to its anti-inflammatory properties. Though the plant has been reported to possess anti-inflammatory antihepatotoxic and analgesic activities, its anticancer potential has not been studied so far. In the present study, we investigated the antiproliferative effects of the total alkaloids isolated from the roots of C. curviflora. The total alkaloid was validated by MTT assay in three cancer cell lines, such as liver cancer cell line-A549, breast cancer cell line-MCF-7 and ovarian cancer cell line -HeLa. Significant antiproliferative effect (IC50 value 3.59±0.14*** µg/mL) was observed in A549 cells, and was taken for further studies. Cell cycle analysis showed that the cells got arrested in sub G0 phase and annexin V-FITC assay revealed that 27.4% cells were in early apoptosis and 7% cells in late apoptosis. The study revealed that the total alkaloids of Chassalia curviflora roots possess significant antiproliferative and apoptotic activity

Antiproliferative effects of total alkaloid extract of roots of Chassaliacurviflora (Wall.) Thwaites on cancer cell lines

Chassaliacurviflora is used in folklore medicines for treating several ailments and infections owing to its anti-inflammatory properties. Though the plant has been reported to possess anti-inflammatory antihepatotoxic and analgesic activities, its anticancer potential has not been studied so far. In the present study, we investigated the antiproliferative effects of the total alkaloids isolated from the roots of C. curviflora.The total alkaloid was validated by MTT assay in three cancer cell lines, such as liver cancer cell line-A549, breast cancer cell line-MCF-7 and ovarian cancer cell line -HeLa. Significant antiproliferative effect (IC50 value 3.59±0.14*** µg/mL) was observed in A549 cells, and was taken for further studies. Cell cycle analysis showed that the cells got arrested in sub G0 phase and annexin V-FITC assay revealed that 27.4% cells were in early apoptosis and 7% cells in late apoptosis. The study revealed that the total alkaloids of Chassaliacurvifloraroots possess significant antiproliferative and apoptotic activit

Macrophages in Breast Cancer: Do Involution Macrophages Account for the Poor Prognosis of Pregnancy-Associated Breast Cancer?

Macrophage influx is associated with negative outcomes for women with breast cancer and has been demonstrated to be required for metastasis of mammary tumors in mouse models. Pregnancy-associated breast cancer is characterized by particularly poor outcomes, however the reasons remain obscure. Recently, post-pregnancy mammary involution has been characterized as having a wound healing signature. We have proposed the involution-hypothesis, which states that the wound healing microenvironment of the involuting gland is tumor promotional. Macrophage influx is one of the prominent features of the involuting gland, identifying the macrophage a potential instigator of tumor progression and a novel target for breast cancer treatment and prevention

Proteomic characterization of HIV-modulated membrane receptors, kinases and signaling proteins involved in novel angiogenic pathways

<p>Abstract</p> <p>Background</p> <p>Kaposi's sarcoma (KS), hemangioma, and other angioproliferative diseases are highly prevalent in HIV-infected individuals. While KS is etiologically linked to the human herpesvirus-8 (HHV8) infection, HIV-patients without HHV-8 and those infected with unrelated viruses also develop angiopathies. Further, HIV-Tat can activate protein-tyrosine-kinase (PTK-activity) of the vascular endothelial growth factor receptor involved in stimulating angiogenic processes. However, Tat by itself or HHV8-genes alone cannot induce angiogenesis <it>in vivo </it>unless specific proteins/enzymes are produced synchronously by different cell-types. We therefore tested a hypothesis that <it>chronic </it>HIV-<it>replication in non-endothelial cells </it>may produce novel factors that provoke angiogenic pathways.</p> <p>Methods</p> <p>Genome-wide proteins from HIV-infected and uninfected T-lymphocytes were tested by subtractive proteomics analyses at various stages of virus and cell growth <it>in vitro </it>over a period of two years. Several thousand differentially regulated proteins were identified by mass spectrometry (MS) and >200 proteins were confirmed in multiple gels. Each protein was scrutinized extensively by protein-interaction-pathways, bioinformatics, and statistical analyses.</p> <p>Results</p> <p>By functional categorization, 31 proteins were identified to be associated with various signaling events involved in angiogenesis. 88% proteins were located in the plasma membrane or extracellular matrix and >90% were found to be essential for regeneration, neovascularization and angiogenic processes during embryonic development.</p> <p>Conclusion</p> <p>Chronic HIV-infection of T-cells produces membrane receptor-PTKs, serine-threonine kinases, growth factors, adhesion molecules and many diffusible signaling proteins that have not been previously reported in HIV-infected cells. Each protein has been associated with endothelial cell-growth, morphogenesis, sprouting, microvessel-formation and other biological processes involved in angiogenesis (p = 10^-4to 10^-12). Bioinformatics analyses suggest that overproduction of PTKs and other kinases in HIV-infected cells has <it>suppressed </it>VEGF/VEGFR-PTK expression and promoted <it>VEGFR-independent </it>pathways. This unique mechanism is similar to that observed in neovascularization and angiogenesis during embryogenesis. Validation of clinically relevant proteins by gene-silencing and translational studies <it>in vivo </it>would identify specific targets that can be used for early diagnosis of angiogenic disorders and future development of inhibitors of angiopathies. This is the first comprehensive study to demonstrate that HIV-infection alone, without any co-infection or treatment, can induce numerous "embryonic" proteins and kinases capable of generating novel <it>VEGF-independent </it>angiogenic pathways.</p