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Molecular and Cellular Biochemistry

, Volume 460, Issue 1–2, pp 175–193 | Cite as

Targeting acquired oncogenic burden in resilient pancreatic cancer: a novel benefit from marine polyphenols

  • Sheeja Aravindan
  • Dinesh Babu Somasundaram
  • Somasundaram T. Somasundaram
  • Mohan Natarajan
  • Terence S. Herman
  • Natarajan AravindanEmail author
Article
  • 101 Downloads

Abstract

The upsurge of marine-derived therapeutics for cancer treatment is evident, with many drugs in clinical use and in clinical trials. Seaweeds harbor large amounts of polyphenols and their anti-cancer benefit is linear to their anti-oxidant activity. Our studies identified three superlative anti-cancer seaweed polyphenol drug candidates (SW-PD). We investigated the acquisition of oncogenic burden in radiation-resilient pancreatic cancer (PC) that could drive tumor relapse, and elucidated the efficacy of SW-PD candidates as adjuvants in genetically diverse in vitro systems and a mouse model of radiation-residual disease. QPCR profiling of 88 oncogenes in therapy-resilient PC cells identified a ‘shared’ activation of 40 oncogenes. SW-PD pretreatment inflicted a significant mitigation of acquired (shared) oncogenic burden, in addition to drug- and cell-line-specific repression signatures. Tissue microarray with IHC of radiation-residual tumors in mice signified acquired cellular localization of key oncoproteins and other critical architects. Conversely, SW-PD treatment inhibited the acquisition of these critical drivers of tumor genesis, dissemination, and evolution. Heightened death of resilient PC cells with SW-PD treatment validated the translation aspects. The results defined the acquisition of oncogenic burden in resilient PC and demonstrated that the marine polyphenols effectively target the acquired oncogenic burden and could serve as adjuvant(s) for PC treatment.

Keywords

Seaweed polyphenols Tumor relapse and recurrence Acquired therapy resistance Adjuvant therapy Oncotargets 

Notes

Acknowledgements

The authors acknowledge the University of Oklahoma SCC-Cancer Tissue Pathology Core for all TMA and IHC services. The authors also acknowledge the OUHSC Office of the Vice President for Research, Staff Editor (Ms. Kathy Kyler) for help in critically reviewing this manuscript.

Author contributions

NA, ST, MN, and TSH contributed to the conception and design of the experiments. SA, DS, and NA performed the experiments and contributed to the acquisition of the data. NA, SA, DS, and MN contributed to data analysis and interpretation of the data. NA and SA drafted the manuscript, and MN, ST, and TSH helped in revising it critically. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Faculty of Marine Sciences, Center for Advanced SciencesAnnamalai UniversityParangipettaiIndia
  2. 2.Stephenson Cancer CenterOklahoma CityUSA
  3. 3.Department of Radiation OncologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  4. 4.Department of PathologyUniversity of Texas Health Sciences Center at San AntonioSan AntonioUSA
  5. 5.Department of PathologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

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