02898nas a2200313   4500008004100000022001400041245015200055210006900207260000800276300000700284490000700291520187700298653001702175653001402192653001802206653001402224653001502238653000902253100001802262700001902280700002002299700001902319700002202338700002002360700001702380700003702397700002102434856012902455       2018                        eng d  a1471-240700aEpoxyazadiradione suppresses breast tumor growth through mitochondrial depolarization and caspase-dependent apoptosis by targeting PI3K/Akt pathway0 aEpoxyazadiradione suppresses breast tumor growth through mitocho  cJAN  a520 v183 a<p>Background: Breast cancer is one of the most commonly diagnosed invasive cancers among women around the world. Among several subtypes, triple negative breast cancer (TNBC) is highly aggressive and chemoresistant. Treatment of TNBC patients has been challenging due to heterogeneity and devoid of well-defined molecular targets. Thus, identification of novel effective and selective agents against TNBC is essential. Methods: We used epoxyazadiradione to assess the cell viability, mitochondrial potential, ROS level, cell migration, apoptosis and protein expression in cell culture models of TNBC MDA-MB-231 and ER+MCF-7 breast cancer cells. The molecular mechanism was examined in two different type of breast cancer cells in response to epoxyazadiradione. We have also analyzed the effect of epoxyazadiradione on breast tumor growth using in vivo mice model. Results: In this study, we for the first time investigated that out of 10 major limonoids isolated from Azadirachta indica, epoxyazadiradione exhibits most potent anti-cancer activity in both TNBC and ER+breast cancer cells. Epoxyazadiradione induces apoptosis and inhibits PI3K/Akt-mediated mitochondrial potential, cell viability, migration and angiogenesis. It also inhibits the expression of pro-angiogenic and pro-metastatic genes such as Cox2, OPN, VEGF and MMP-9 in these cells. Furthermore, epoxyazadiradione attenuates PI3K/Akt- mediated AP-1 activation. Our in vivo data revealed that epoxyazadiradione suppresses breast tumor growth and angiogenesis in orthotopic NOD/SCID mice model. Conclusion: Our findings demonstrate that epoxyazadiradione inhibits PI3K/Akt-dependent mitochondrial depolarisation, induces apoptosis and attenuates cell migration, angiogenesis and breast tumor growth suggesting that this compound may act as a potent therapeutic agent for the management of breast cancer.</p>10aAngiogenesis10aApoptosis10aBreast cancer10aLimonoids10aMetastasis10aPI3K1 aKumar, Dhiraj1 aHaldar, Saikat1 aGorain, Mahadeo1 aKumar, Santosh1 aMulani, Fayaj, A.1 aYadav, Amit, S.1 aMiele, Lucio1 aThulasiram, Hirekodathakallu, V.1 aKundu, Gopal, C.  uhttps://library.ncl.res.in/content/epoxyazadiradione-suppresses-breast-tumor-growth-through-mitochondrial-depolarization-and01458nas a2200217   4500008004100000022001400041245006500055210006500120260000900185300001400194490000900208520077500217653002800992653001501020653001601035653000801051653004701059100002101106700002101127856009201148       2021                        eng d  a1434-193X00aTotal synthesis of a hypothetical macroketone of migrastatin0 aTotal synthesis of a hypothetical macroketone of migrastatin  cJUN   a3050-30530 v20213 aDanishefsky's macroketone, a simplified analogue of natural product Migrastatin, is one of the lead compounds with potent cancer cell migration inhibition potential. Different biological assays suggest fascin protein as the potential target. Although it was indicated through X-ray co-crystallography where the concerned macroketone analogue was found to bind in the actin-binding sites of fascin, there was a structural discrepancy, as the X-ray co-crystal structure suggested an E-olefin along with inversion of methyl stereochemistry from that of Danishefsky's macroketone. Here, we have accomplished the total synthesis of the `hypothetical macroketone' for the first time. The TiCl4 mediated vinylogous Mukaiyama aldol reaction is the key step in present synthesis.10aHypothetical mecroketon10aMetastasis10aMigrastatin10aRCM10avinylogous Mukaiyama aldol reaction (VMAR)1 aChoudhury, Rahul1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/total-synthesis-hypothetical-macroketone-migrastatin02992nas a2200349   4500008004100000022001400041245010700055210006900162260000900231300001100240490000700251520191400258653000902172653001402181653001602195653001502211653001302226100001502239700001402254700002202268700002402290700002002314700001902334700002202353700001802375700002202393700002302415700002502438700002602463700002202489856013102511       2021                        eng d  a2234-943X00aUnbiased phenotype-based screen identifies therapeutic agents selective for metastatic prostate cancer0 aUnbiased phenotypebased screen identifies therapeutic agents sel  cMAR   a5941410 v103 a<p>In American men, prostate cancer is the second leading cause of cancer-related death. Dissemination of prostate cancer cells to distant organs significantly worsens patients' prognosis, and currently there are no effective treatment options that can cure advanced-stage prostate cancer. In an effort to identify compounds selective for metastatic prostate cancer cells over benign prostate cancer cells or normal prostate epithelial cells, we applied a phenotype-based in vitro drug screening method utilizing multiple prostate cancer cell lines to test 1,120 different compounds from a commercial drug library. Top drug candidates were then examined in multiple mouse xenograft models including subcutaneous tumor growth, experimental lung metastasis, and experimental bone metastasis assays. A subset of compounds including fenbendazole, fluspirilene, clofazimine, niclosamide, and suloctidil showed preferential cytotoxicity and apoptosis towards metastatic prostate cancer cells in vitro and in vivo. The bioavailability of the most discerning agents, especially fenbendazole and albendazole, was improved by formulating as micelles or nanoparticles. The enhanced forms of fenbendazole and albendazole significantly prolonged survival in mice bearing metastases, and albendazole-treated mice displayed significantly longer median survival times than paclitaxel-treated mice. Importantly, these drugs effectively targeted taxane-resistant tumors and bone metastases - two common clinical conditions in patients with aggressive prostate cancer. In summary, we find that metastatic prostate tumor cells differ from benign prostate tumor cells in their sensitivity to certain drug classes. Taken together, our results strongly suggest that albendazole, an anthelmintic medication, may represent a potential adjuvant or neoadjuvant to standard therapy in the treatment of disseminated prostate cancer.</p>
10abone10acarcinoma10adrug-screen10aMetastasis10aProstate1 aChung, Ivy1 aZhou, Kun1 aBarrows, Courtney1 aBanyard, Jacqueline1 aWilson, Arianne1 aRummel, Nathan1 aMizokami, Atsushi1 aBasu, Sudipta1 aSengupta, Poulomi1 aShaikh, Badaruddin1 aSengupta, Shiladitya1 aBielenberg, Diane, R.1 aZetter, Bruce, R.  uhttps://library.ncl.res.in/content/unbiased-phenotype-based-screen-identifies-therapeutic-agents-selective-metastatic-prostate