Hormophysa triquerta polyphenol, an elixir that deters CXCR4- and COX2-dependent dissemination destiny of treatment-resistant pancreatic cancer cells
| Autor: | Sheeja Aravindan, Terence S. Herman, Kathiresan Kandasamy, Somasundaram S. Thirugnanasambandan, Natarajan Aravindan, Satish Kumar Ramraj, Dinesh Babu Somasundaram |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
tumor relapse and recurrence Pathology medicine.medical_specialty Receptors CXCR4 Neoplasm Residual pancreatic cancer residual pancreatic cancer Down-Regulation MMP9 Phaeophyta CXCR4 Metastasis Transcriptome 03 medical and health sciences Mice 0302 clinical medicine Cell Movement Pancreatic cancer Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness seaweed polyphenols business.industry Plant Extracts Gene Expression Profiling Cancer Polyphenols Cell migration medicine.disease Seaweed Xenograft Model Antitumor Assays In vitro Gene Expression Regulation Neoplastic Pancreatic Neoplasms 030104 developmental biology Oncology tumor invasion and metastasis Cyclooxygenase 2 Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Sheeja Aravindan 1,2 , Satishkumar Ramraj 3 , Kathiresan Kandasamy 1 , Somasundaram S. Thirugnanasambandan 1 , Dinesh Babu Somasundaram 3 , Terence S. Herman 2,3 and Natarajan Aravindan 3 1 Department of Marine Sciences, Center of Advanced Study in Marine Biology, Annamalai University, Parangipettai, TN, India 2 Stephenson Cancer Center, Oklahoma City, OK, USA 3 Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Correspondence to: Natarajan Aravindan, email: // Keywords : pancreatic cancer; seaweed polyphenols; tumor invasion and metastasis; residual pancreatic cancer; tumor relapse and recurrence Received : October 11, 2016 Accepted : November 23, 2016 Published : December 10, 2016 Abstract Therapy-resistant pancreatic cancer (PC) cells play a crucial role in tumor relapse, recurrence, and metastasis. Recently, we showed the anti-PC potential of an array of seaweed polyphenols and identified efficient drug deliverables. Herein, we investigated the benefit of one such deliverable, Hormophysa triquerta polyphenol (HT-EA), in regulating the dissemination physiognomy of therapy-resistant PC cells in vitro ,and residual PC in vivo . Human PC cells exposed to ionizing radiation (IR), with/without HT-EA pre-treatment were examined for the alterations in the tumor invasion/metastasis (TIM) transcriptome (93 genes, QPCR-profiling). Utilizing a mouse model of residual PC, we investigated the benefit of HT-EA in the translation regulation of crucial TIM targets (TMA-IHC). Radiation activated 30, 50, 15, and 38 TIM molecules in surviving Panc-1, Panc-3.27, BxPC3, and MiaPaCa-2 cells. Of these, 15, 44, 12, and 26 molecules were suppressed with HT-EA pre-treatment. CXCR4 and COX2 exhibited cell-line-independent increases after IR, and was completely suppressed with HT-EA, across all PC cells. HT-EA treatment resulted in translational repression of IR-induced CXCR4, COX2, β-catenin, MMP9, Ki-67, BAPX, PhPT-1, MEGF10, and GRB10 in residual PC. Muting CXCR4 or COX2 regulated the migration/invasion potential of IR-surviving cells, while forced expression of CXCR4 or COX2 significantly increased migration/invasion capabilities of PC cells. Further, treatment with HT-EA significantly inhibited IR-induced and CXCR4/COX2 forced expression-induced PC cell migration/invasion. This study (i) documents the TIM blueprint in therapy-resistant PC cells, (ii) defines the role of CXCR4 and COX2 in induced metastatic potential, and (iii) recognizes the potential of HT-EA in deterring the CXCR4/COX2-dependent dissemination destiny of therapy-resistant residual PC cells. |
| Databáze: | OpenAIRE |
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