title: Hormophysa triquerta polyphenol, an elixir that deters CXCR4- and COX2-dependent dissemination destiny of treatment-resistant pancreatic cancer cells.
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.
authors.affiliation: Department of Marine Sciences, Center of Advanced Study in Marine Biology, Annamalai University, Parangipettai, TN, India.|Stephenson Cancer Center, Oklahoma City, OK, USA.
authors.forename: Sheeja
authors.initials: S
authors.lastname: Aravindan
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Satishkumar
authors.initials: S
authors.lastname: Ramraj
authors.affiliation: Department of Marine Sciences, Center of Advanced Study in Marine Biology, Annamalai University, Parangipettai, TN, India.
authors.forename: Kathiresan
authors.initials: K
authors.lastname: Kandasamy
authors.affiliation: Department of Marine Sciences, Center of Advanced Study in Marine Biology, Annamalai University, Parangipettai, TN, India.
authors.forename: Somasundaram S
authors.initials: SS
authors.lastname: Thirugnanasambandan
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Dinesh Babu
authors.initials: DB
authors.lastname: Somasundaram
authors.affiliation: Stephenson Cancer Center, Oklahoma City, OK, USA.|Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Terence S
authors.initials: TS
authors.lastname: Herman
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Aravindan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D018365:Neoplasm, Residual; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D000459:Phaeophyceae / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry; D059808:Polyphenols / Q000008:administration & dosage* / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000235:genetics*; D012624:Seaweed / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: C527276:CXCR4 protein, human; D010936:Plant Extracts; D059808:Polyphenols; D019718:Receptors, CXCR4; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: pancreatic cancer; residual pancreatic cancer; seaweed polyphenols; tumor invasion and metastasis; tumor relapse and recurrence