Posters
Targeting RNA Polymerase I suppresses growth of pancreatic cancer
Presentation Type
Poster
Discipline Track
Clinical Science
Abstract Type
Research/Clinical
Abstract
Background: Dysregulation of ribosome biogenesis was observed in various cancer types including pancreatic cancer (PanCa).Therefore, strategically targeting ribosome biogenesis could be a novel approach for pancreatic cancer treatment. One such approach is to targe tribosome biogenesis is via small molecule inhibitors of RNA Polymerase Ias these inhibitors have shown promising anti-cancer activity. In this study, we for the first time, evaluated the therapeutic effect of a novel RNA polymerase I inhibitor (BMH-21) against PanCa.
Methods and Results: We observed differential constitutive expression of RPA-194 in human PanCa cells when compared with normal HPDE cells. BMH-21 significantly inhibited expression of RPA194 in PanCa cells as determined by WB and confocal microscopy analysis. BMH-21 induced the apoptosis and inhibited growth of various PanCa cells as determined by MTT assay and flow cytometry. BMH-21 treatment inhibited colony formation potential and metastatic phenotypes of various PanCa cells as examined by colony formation and atomic force microscopy analyses.BMH-21 significantly (P<0.01) downregulates the phosphorylation of AKT (Ser473) and WNK-1 (Thr60) kinases and Stat3 phosphorylation at Ser727 and upregulates pChk2 kinase in PanCa cells.BMH-21(2 mg/kg i.p) inhibited pancreatic tumor growth in an orthotopic xenograft mouse model. Excised tumor tissues of BMH-21 treated mice showed decrease expression of RPA194 and ki67as compared to vehicle treated group.
Conclusion: Our results suggest that BMH-21 is a novel drug for targeting ribosome biogenesis and could be used for the treatment of pancreatic cancer.
Academic/Professional Position
Graduate Student
Mentor/PI Department
Immunology and Microbiology
Recommended Citation
Perez, Carlos; Massey, Andrew; Shahriar, Asif; Anning, Emmanuel; Kashyap, Vivek K.; Chauhan, Neeraj; Dhasmana, Anupam; Tripathi, Manish; Chauhan, Subhash C.; and Hafeez, Bilal B., "Targeting RNA Polymerase I suppresses growth of pancreatic cancer" (2023). Research Symposium. 122.
https://scholarworks.utrgv.edu/somrs/theme1/posters/122
Targeting RNA Polymerase I suppresses growth of pancreatic cancer
Background: Dysregulation of ribosome biogenesis was observed in various cancer types including pancreatic cancer (PanCa).Therefore, strategically targeting ribosome biogenesis could be a novel approach for pancreatic cancer treatment. One such approach is to targe tribosome biogenesis is via small molecule inhibitors of RNA Polymerase Ias these inhibitors have shown promising anti-cancer activity. In this study, we for the first time, evaluated the therapeutic effect of a novel RNA polymerase I inhibitor (BMH-21) against PanCa.
Methods and Results: We observed differential constitutive expression of RPA-194 in human PanCa cells when compared with normal HPDE cells. BMH-21 significantly inhibited expression of RPA194 in PanCa cells as determined by WB and confocal microscopy analysis. BMH-21 induced the apoptosis and inhibited growth of various PanCa cells as determined by MTT assay and flow cytometry. BMH-21 treatment inhibited colony formation potential and metastatic phenotypes of various PanCa cells as examined by colony formation and atomic force microscopy analyses.BMH-21 significantly (P<0.01) downregulates the phosphorylation of AKT (Ser473) and WNK-1 (Thr60) kinases and Stat3 phosphorylation at Ser727 and upregulates pChk2 kinase in PanCa cells.BMH-21(2 mg/kg i.p) inhibited pancreatic tumor growth in an orthotopic xenograft mouse model. Excised tumor tissues of BMH-21 treated mice showed decrease expression of RPA194 and ki67as compared to vehicle treated group.
Conclusion: Our results suggest that BMH-21 is a novel drug for targeting ribosome biogenesis and could be used for the treatment of pancreatic cancer.