Indolo-pyrido-isoquinolin based alkaloid inhibits growth, invasion and migration of breast cancer cells via activation of p53-miR34a axis
The tumor suppressor p53 plays a critical role in suppressing cancer growth and progression and is an attractive target for the development of new targeted therapies. We synthesized several indolo-pyrido-isoquinolin based alkaloids to activate p53 function and examined their therapeutic efficacy using NCI-60 screening. Here, we provide molecular evidence that one of these compounds, 11-methoxy-2,3,4,13-tetrahydro-1H-indolo[2 ′,3′:3,4]pyrido[1,2-b]isoquinolin-6-ylium-bromide (termed P18 or NSC-768219) inhibits growth and clonogenic potential of cancer cells. (Source: Molecular Oncology)
Source: Molecular Oncology - May 19, 2016 Category: Cancer & Oncology Authors: Dimiter B. Avtanski, Arumugam Nagalingam, Joseph E. Tomaszewski, Prabhakar Risbood, Michael J. Difillippantonio, Neeraj K. Saxena, Sanjay V. Malhotra, Dipali Sharma Source Type: research
Indolo-pyrido-isoquinolin based alkaloid inhibits growth, invasion and migration of breast cancer cells via activation of p53-miR34a axis
The tumor suppressor p53 plays a critical role in suppressing cancer growth and progression and is an attractive target for the development of new targeted therapies. We synthesized several indolo-pyrido-isoquinolin based alkaloids to activate p53 function and examined their therapeutic efficacy using NCI-60 screening. Here, we provide molecular evidence that one of these compounds, 11-Methoxy-2,3,4,13-tetrahydro-1H-indolo[2',3':3,4]pyrido[1,2-b]isoquinolin-6-ylium-bromide (termed P18 or NSC-768219) inhibits growth and clonogenic potential of cancer cells. (Source: Molecular Oncology)
Source: Molecular Oncology - May 19, 2016 Category: Cancer & Oncology Authors: Dimiter B. Avtanski, Arumugam Nagalingam, Joseph E. Tomaszewski, Prabhakar Risbood, Michael J. Difillippantonio, Neeraj K. Saxena, Sanjay V. Malhotra, Dipali Sharma Source Type: research
Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors
The synthetic steroid mifepristone blocks the growth of ovarian cancer cells, yet the mechanism driving such effect is not entirely understood. Unbiased genomic and proteomic screenings using ovarian cancer cell lines of different genetic backgrounds and sensitivities to platinum led to the identification of two key genes upregulated by mifepristone and involved in the unfolded protein response (UPR): the master chaperone of the endoplasmic reticulum (ER), glucose regulated protein (GRP) of 78 kDa, and the CCAAT/enhancer binding protein homologous transcription factor (CHOP). (Source: Molecular Oncology)
Source: Molecular Oncology - May 16, 2016 Category: Cancer & Oncology Authors: Lei Zhang, Maria B. Hapon, Alicia A. Goyeneche, Rekha Srinivasan, Carlos D. Gamarra-Luques, Eduardo A. Callegari, Donis D. Drappeau, Erin J. Terpstra, Bo Pan, Jennifer R. Knapp, Jeremy Chien, Xuejun Wang, Kathleen M. Eyster, Carlos M. Telleria Source Type: research
Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity
FK506-binding proteins are members of the immunophilin family of proteins. Those immunophilins associated to the 90-kDa-heat-shock protein, Hsp90, have been proposed as potential modulators of signalling cascade factors chaperoned by Hsp90. FKBP51 and FKBP52 are the best characterized Hsp90-bound immunophilins first described associated to steroid-receptors. The reverse transcriptase subunit of telomerase, hTERT, is also an Hsp90 client-protein and is highly expressed in cancer cells, where it is required to compensate the loss of telomeric DNA after each successive cell division. (Source: Molecular Oncology)
Source: Molecular Oncology - May 16, 2016 Category: Cancer & Oncology Authors: Mariana Lagadari, Nadia R. Zgajnar, Luciana I. Gallo, Mario D. Galigniana Source Type: research
Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors
The synthetic steroid mifepristone blocks the growth of ovarian cancer cells, yet the mechanism driving such effect is not entirely understood. Unbiased genomic and proteomic screenings using ovarian cancer cell lines of different genetic backgrounds and sensitivities to platinum led to the identification of two key genes upregulated by mifepristone and involved in the unfolded protein response (UPR): the master chaperone of the endoplasmic reticulum (ER), glucose regulated protein (GRP) of 78 kDa, and the CCAAT/enhancer binding protein homologous transcription factor (CHOP). (Source: Molecular Oncology)
Source: Molecular Oncology - May 16, 2016 Category: Cancer & Oncology Authors: Lei Zhang, Maria B. Hapon, Alicia A. Goyeneche, Rekha Srinivasan, Carlos D. Gamarra-Luques, Eduardo A. Callegari, Donis D. Drappeau, Erin J. Terpstra, Bo Pan, Jennifer R. Knapp, Jeremy Chien, Xuejun Wang, Kathleen M. Eyster, Carlos M. Telleria Source Type: research
Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity
FK506-binding proteins are members of the immunophilin family of proteins. Those immunophilins associated to the 90-kDa-heat-shock protein, Hsp90, have been proposed as potential modulators of signalling cascade factors chaperoned by Hsp90. FKBP51 and FKBP52 are the best characterized Hsp90-bound immunophilins first described associated to steroid-receptors. The reverse transcriptase subunit of telomerase, hTERT, is also an Hsp90 client-protein and is highly expressed in cancer cells, where it is required to compensate the loss of telomeric DNA after each successive cell division. (Source: Molecular Oncology)
Source: Molecular Oncology - May 16, 2016 Category: Cancer & Oncology Authors: Mariana Lagadari, Nadia R. Zgajnar, Luciana I. Gallo, Mario D. Galigniana Source Type: research
Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors
The synthetic steroid mifepristone blocks the growth of ovarian cancer cells, yet the mechanism driving such effect is not entirely understood. Unbiased genomic and proteomic screenings using ovarian cancer cell lines of different genetic backgrounds and sensitivities to platinum led to the identification of two key genes upregulated by mifepristone and involved in the unfolded protein response (UPR): the master chaperone of the endoplasmic reticulum (ER), glucose regulated protein (GRP) of 78 kDa, and the CCAAT/enhancer binding protein homologous transcription factor (CHOP). (Source: Molecular Oncology)
Source: Molecular Oncology - May 16, 2016 Category: Cancer & Oncology Authors: Lei Zhang, Maria B. Hapon, Alicia A. Goyeneche, Rekha Srinivasan, Carlos D. Gamarra-Luques, Eduardo A. Callegari, Donis D. Drappeau, Erin J. Terpstra, Bo Pan, Jennifer R. Knapp, Jeremy Chien, Xuejun Wang, Kathleen M. Eyster, Carlos M. Telleria Source Type: research
Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity
FK506-binding proteins are members of the immunophilin family of proteins. Those immunophilins associated to the 90-kDa-heat-shock protein, Hsp90, have been proposed as potential modulators of signalling cascade factors chaperoned by Hsp90. FKBP51 and FKBP52 are the best characterized Hsp90-bound immunophilins first described associated to steroid-receptors. The reverse transcriptase subunit of telomerase, hTERT, is also an Hsp90 client-protein and is highly expressed in cancer cells, where it is required to compensate the loss of telomeric DNA after each successive cell division. (Source: Molecular Oncology)
Source: Molecular Oncology - May 16, 2016 Category: Cancer & Oncology Authors: Mariana Lagadari, Nadia R. Zgajnar, Luciana I. Gallo, Mario D. Galigniana Source Type: research
Editorial Board
(Source: Molecular Oncology)
Source: Molecular Oncology - April 30, 2016 Category: Cancer & Oncology Source Type: research
Heterogeneous estrogen receptor expression in circulating tumor cells suggests diverse mechanisms of fulvestrant resistance
Fulvestrant is a dose dependent selective estrogen receptor (ER) down-regulator (SERD) used in ER-positive metastatic breast cancer (MBC). Nearly all patients develop resistance. We performed molecular analysis of circulating tumor cells (CTC) to gain insight into fulvestrant resistance.Preclinical studies were performed with cultured breast cancer cells spiked into human blood and analyzed on the CellSearch ® system. Clinical data are limited to a subset of patients with ER-positive MBC from a previously reported pilot trial whose disease was progressing on fulvestrant (N = 7) or aromatase inhibitors (AIs) (N = 10). ...
Source: Molecular Oncology - April 28, 2016 Category: Cancer & Oncology Authors: Costanza Paoletti, Jose M. Larios, Maria C. Mu ñiz, Kimberly Aung, Emily M. Cannell, Elizabeth P. Darga, Kelley M. Kidwell, Dafydd G. Thomas, Nahomi Tokudome, Martha E. Brown, Mark C. Connelly, David A. Chianese, Anne F. Schott, N. Lynn Henry, James M. R Source Type: research
Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer
The majority of pancreatic cancer (PC) patients are clinically presented with obstructive jaundice with elevated levels of circulatory bilirubin and alkaline phosphatases. In the current study, we examined the implications of bile acids (BA), an important component of bile, on the pathophysiology of PC and investigated their mechanistic association in tumor-promoting functions. Integration of results from PC patient samples and autochthonous mouse models showed an elevated levels of BA (p < 0.05) in serum samples compared to healthy controls. (Source: Molecular Oncology)
Source: Molecular Oncology - April 28, 2016 Category: Cancer & Oncology Authors: Suhasini Joshi, Eric Cruz, Satyanarayana Rachagani, Sushovan Guha, Randall E. Brand, Moorthy P. Ponnusamy, Sushil Kumar, Surinder K. Batra Source Type: research
Heterogeneous estrogen receptor expression in circulating tumor cells suggests diverse mechanisms of fulvestrant resistance
Fulvestrant is a dose dependent selective estrogen receptor (ER) down-regulator (SERD) used in ER-positive metastatic breast cancer (MBC). Nearly all patients develop resistance. We performed molecular analysis of circulating tumor cells (CTC) to gain insight into fulvestrant resistance.Preclinical studies were performed with cultured breast cancer cells spiked into human blood and analyzed on the CellSearch® system. Clinical data are limited to a subset of patients with ER-positive MBC from a previously reported pilot trial whose disease was progressing on fulvestrant (N=7) or aromatase inhibitors (AIs) (N=10). (Source: Molecular Oncology)
Source: Molecular Oncology - April 28, 2016 Category: Cancer & Oncology Authors: Costanza Paoletti, Jose M. Larios, Maria C. Muñiz, Kimberly Aung, Emily M. Cannell, Elizabeth P. Darga, Kelley M. Kidwell, Dafydd G. Thomas, Nahomi Tokudome, Martha E. Brown, Mark C. Connelly, David A. Chianese, Anne F. Schott, N. Lynn Henry, James M. Ra Source Type: research
Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer
The majority of pancreatic cancer (PC) patients are clinically presented with obstructive jaundice with elevated levels of circulatory bilirubin and alkaline phosphatases. In the current study, we examined the implications of bile acids (BA), an important component of bile, on the pathophysiology of PC and investigated their mechanistic association in tumor-promoting functions. Integration of results from PC patient samples and autochthonous mouse models showed an elevated levels of BA (p (Source: Molecular Oncology)
Source: Molecular Oncology - April 28, 2016 Category: Cancer & Oncology Authors: Suhasini Joshi, Eric Cruz, Satyanarayana Rachagani, Sushovan Guha, Randall E. Brand, Moorthy P. Ponnusamy, Sushil Kumar, Surinder K. Batra Source Type: research
MDM2 antagonist nutlin-3a sensitizes tumors to V-ATPase inhibition
Treating cancer is one of the big challenges of this century and it has become evident that single chemotherapeutic treatment is rarely effective. As tumors often carry multiple mutations using combination therapy which addresses different targets seems therefore more beneficial. One of the most frequently mutated genes in tumors is the tumor suppressor p53. Significant work has been put in the development of p53 activators, which are now in clinical studies against diverse cancers. Recently, we could show that inhibition of V-ATPase, a multisubunit proton pump, by archazolid induces p53 protein levels in cancer cells. (So...
Source: Molecular Oncology - April 25, 2016 Category: Cancer & Oncology Authors: Lina S. Schneider, Melanie Ulrich, Thorsten Lehr, Dirk Menche, Rolf M üller, Karin von Schwarzenberg Source Type: research
MDM2 antagonist nutlin-3a sensitizes tumors to V-ATPase inhibition
Treating cancer is one of the big challenges of this century and it has become evident that single chemotherapeutic treatment is rarely effective. As tumors often carry multiple mutations using combination therapy which addresses different targets seems therefore more beneficial. One of the most frequently mutated genes in tumors is the tumor suppressor p53. Significant work has been put in the development of p53 activators, which are now in clinical studies against diverse cancers. Recently, we could show that inhibition of V-ATPase1, a multisubunit proton pump, by archazolid induces p53 protein levels in cancer cells. (S...
Source: Molecular Oncology - April 25, 2016 Category: Cancer & Oncology Authors: Lina S. Schneider, Melanie Ulrich, Thorsten Lehr, Dirk Menche, Rolf Müller, Karin von Schwarzenberg Source Type: research
