Article: Synthesis and anticancer effects of pongamol derivatives on mitogen signaling and cell cycle kinasesR Ranga, Rao @bullet, Vishal Chaturvedi, bullet K Suresh, Babu @bullet, P Prabhakar Reddy, bullet V Rama, Subba Rao, bullet P Sreekanth, bullet A S Sreedhar, bullet J Madhusudana Rao[show abstract] [hide abstract]
ABSTRACT: A series of oxazole and pyrazole derivatives of pongamol (1) were designed and synthesized to examine their anti-cancer activity. The cytotoxicity of these com-pounds was examined in three different human tumor cell lines, IMR-32, HeLa and Jurkat. Although all compounds tested were quite effective than the pongamol against all the three different types of cancer cell lines examined, the compounds (2), (5), and (6) were found to be the most active compounds of this series.Medicinal Chemistry Research 01/2012; · 1.27 Impact Factor
Australian Biochemist. 12/2011; 42(3):8-10.
Article: Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells.Chaturvedi Vishal, Jonnala Ujwal Kumar, Cherukuvada Veera Brahmendra Swamy, Rangaraj Nandini, Gunda Srinivas, Rathinam Kumaresan, Singh Shashi, Amere Subbarao Sreedhar[show abstract] [hide abstract]
ABSTRACT: Inhibiting Hsp90 chaperone roles using 17AAG induces cytostasis or apoptosis in tumor cells through destabilization of several mutated cancer promoting proteins. Although mitochondria are central in deciding the fate of cells, 17AAG induced effects on tumor cell mitochondria were largely unknown. Here, we show that Hsp90 inhibition with 17AAG first affects mitochondrial integrity in different human tumor cells, neuroblastoma, cervical cancer and glial cells. Using human neuroblastoma tumor cells, we found the early effects associated with a change in mitochondrial membrane potential, elongation and engorgement of mitochondria because of an increased matrix vacuolization. These effects are specific to Hsp90 inhibition as other chemotherapeutic drugs did not induce similar mitochondrial deformity. Further, the effects are independent of oxidative damage and cytoarchitecture destabilization since cytoskeletal disruptors and mitochondrial metabolic inhibitors also do not induce similar deformity induced by 17AAG. The 1D PAGE LC MS/MS mitochondrial proteome analysis of 17AAG treated human neuroblastoma cells showed a loss of 61% proteins from membrane, metabolic, chaperone and ribonucleoprotein families. About 31 unmapped protein IDs were identified from proteolytic processing map using Swiss-Prot accession number, and converted to the matching gene name searching the ExPASy proteomics server. Our studies display that Hsp90 inhibition effects at first embark on mitochondria of tumor cells and compromise mitochondrial integrity.Drug Target Insights 01/2011; 5:11-32.
Article: Pharmacological inhibition of Hsp90 as a novel antitumor strategy to target cytoarchitecture through extracellular matrix signaling.Vishal Chaturvedi, Jonnala Ujwal Kumar, Khande Rao Paithankar, Perumal Vanathi, Amere Subbarao Sreedhar[show abstract] [hide abstract]
ABSTRACT: Pharmacological inhibition of Hsp90 in tumor cells induces anticancer effects through the destabilization of several oncogenic signaling molecules. Although there were reports that Hsp90 inhibition compromises cellular integrity, how this affects the cell adhesion through extracellular matrix (ECM) and integrin signaling is not known. Using human neuroblastoma (IMR-32), cervical (HeLa) and breast (MCF-7) cancer cells, and mouse embryonic carcinoma (PCC-4) cells, and using different substratum, glass, plastic, fibronectin, and matrigel, we demonstrate 17AAG induced alterations in integrin cross-linking with the actin cytoskeleton. The 17AAG treatment of cells resulted in decreased mRNA levels and confined surface expression of three major beta1 family of integrins namely α2, α3, and α5 in IMR-32, HeLa and PCC-4 cells, but showed induced mRNA levels and surface expression in MCF-7 cells. Loss of surface expression of integrins correlated with inhibition of focal adhesion kinase (FAK) and mitogen regulated kinase (ERK1/2) activities, in contrast, induced integrin expression in MCF-7 correlated with activation of these kinases. Prolonged treatment but not the pretreatment (2 h) with 17AAG resulted in destabilized actin cytoskeleton, delayed wound repair, and limited colony forming ability of tumor cells on soft agar. Conclusively, we show that Hsp90 inhibition targets cell adhesion, which may relate to the inhibition of integrin signaling and inhibition of integrin-cytoskeleton crosslinking.Medicinal chemistry (Shāriqah (United Arab Emirates)) 06/2011; 7(5):454-65. · 1.64 Impact Factor
Article: Hsp90 inhibition induces destabilization of actin cytoskeleton in tumor cells: functional significance of Hsp90 interaction with F-actin.Vishal Chaturvedi, A S SreedharAsian Pacfic Journal of Tropical Medicine. 01/2010;
Role of extracellular matrix in muscle repair and regeneration