Abilities of β-Estradiol to interact with chemotherapeutic drugs, signal transduction inhibitors and nutraceuticals and alter the proliferation of pancreatic cancer cells

Shaw M Akula; Saverio Candido; Stephen L Abrams; Linda S Steelman; Kvin Lertpiriyapong; Lucio Cocco; Giulia Ramazzotti; Stefano Ratti; Matilde Y Follo; Alberto M Martelli; Ramiro M Murata; Pedro L Rosalen; Bruno Bueno-Silva; Severino Matias de Alencar; Marco Falasca; Giuseppe Montalto; Melchiorre Cervello; Monica Notarbartolo; Agnieszka Gizak; Dariusz Rakus; Massimo Libra; James A McCubrey

doi:10.1016/j.jbior.2019.100672

Abilities of β-Estradiol to interact with chemotherapeutic drugs, signal transduction inhibitors and nutraceuticals and alter the proliferation of pancreatic cancer cells

Adv Biol Regul. 2020 Jan:75:100672. doi: 10.1016/j.jbior.2019.100672. Epub 2019 Oct 18.

Authors

Shaw M Akula¹, Saverio Candido², Stephen L Abrams¹, Linda S Steelman¹, Kvin Lertpiriyapong³, Lucio Cocco⁴, Giulia Ramazzotti⁴, Stefano Ratti⁴, Matilde Y Follo⁴, Alberto M Martelli⁴, Ramiro M Murata⁵, Pedro L Rosalen⁶, Bruno Bueno-Silva⁷, Severino Matias de Alencar⁸, Marco Falasca⁹, Giuseppe Montalto¹⁰, Melchiorre Cervello¹¹, Monica Notarbartolo¹², Agnieszka Gizak¹³, Dariusz Rakus¹³, Massimo Libra², James A McCubrey¹⁴

Affiliations

¹ Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, 27858, USA.
² Department of Biomedical and Biotechnological Sciences, Oncological, Clinical and General Pathology Section, University of Catania, Catania, Italy; Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania, Italy.
³ Center of Comparative Medicine and Pathology, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medicine and the Hospital for Special Surgery, New York City, New York, USA.
⁴ Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
⁵ Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, 27858, USA; Department of Foundational Sciences, School of Dental Medicine, East Carolina University, USA.
⁶ Department of Physiological Sciences, Piracicaba Dental School, State University of Campinas, Piracicaba, Brazil.
⁷ Department of Physiological Sciences, Piracicaba Dental School, State University of Campinas, Piracicaba, Brazil; Dental Research Division, Guarulhos University, Guarulhos, Brazil.
⁸ Universidade de São Paulo - USP, "Luiz de Queiroz" College of Agriculture, São Paulo, Brazil.
⁹ Metabolic Signalling Group, School of Pharmacy & Biomedical Sciences, Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Perth, Western Australia, 6102, Australia.
¹⁰ Dipartimento di Promozione Della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza (PROMISE), University of Palermo, Palermo, Italy; Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo, Italy.
¹¹ Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo, Italy.
¹² Department of Biological, Chemical and Pharmaceutical Science and Technology (STEBICEF), University of Palermo, Palermo, Italy.
¹³ Department of Molecular Physiology and Neurobiology, Wroclaw University, Wroclaw, Poland.
¹⁴ Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, 27858, USA. Electronic address: mccubreyj@ecu.edu.

PMID: 31685431
DOI: 10.1016/j.jbior.2019.100672

Abstract

Improving the effects of chemotherapy and reducing the side effects are important goals in cancer research. Various approaches have been examined to enhance the effectiveness of chemotherapy. For example, signal transduction inhibitors or hormonal based approaches have been included with chemo- or radio-therapy. MIA-PaCa-2 and BxPC-3 pancreatic ductal adenocarcinoma (PDAC) cells both express the estrogen receptor (ER). The effects of β-estradiol on the growth of PDAC cells has not been examined yet the ER is expressed in PDAC cells. We have examined the effects of combining β-estradiol with chemotherapeutic drugs, signal transcription inhibitors, natural products and nutraceuticals on PDAC. In most cases, inclusion of β-estradiol with chemotherapeutic drugs increased chemosensitivity. These results indicate some approaches involving β-estradiol which may be used to increase the effectiveness of chemotherapeutic and other drugs on the growth of PDAC.

Keywords: Chemotherapeutic drugs; Natural products; Nutraceuticals; Pancreatic cancer; β-Estradiol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
Carcinoma, Pancreatic Ductal* / drug therapy
Carcinoma, Pancreatic Ductal* / metabolism
Carcinoma, Pancreatic Ductal* / pathology
Cell Line, Tumor
Cell Proliferation / drug effects*
Dietary Supplements*
Estradiol / pharmacology*
Female
Food-Drug Interactions
Humans
Middle Aged
Pancreatic Neoplasms* / drug therapy
Pancreatic Neoplasms* / metabolism
Pancreatic Neoplasms* / pathology
Signal Transduction / drug effects*

Substances

Antineoplastic Agents
Estradiol