Effects of Fentanyl on pancreatic cancer cell proliferation and cancer stem cell differentiation

Feyzi Celik; Tugce Duran

doi:10.14715/cmb/2019.65.7.5

Issue

Vol. 65 No. 7: Issue 7

Issue Published : October 14, 2019

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

Effects of Fentanyl on pancreatic cancer cell proliferation and cancer stem cell differentiation

https://doi.org/10.14715/cmb/2019.65.7.5

Feyzi Celik

Department of Anesthesiology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey

http://orcid.org/0000-0001-5986-8785

Tugce Duran

Department of Medical Genetics, Faculty of Medicine, KTO Karatay University, Konya, Turkey

http://orcid.org/0000-0002-7353-4527

Corresponding Author(s) : Feyzi Celik

drfeyzicelik21@gmail.com

Cellular and Molecular Biology, Vol. 65 No. 7: Issue 7
Article Published : September 30, 2019

Abstract

Pancreatic cancer is one of the most aggressive cancer due to the late diagnosis and failure to respond to the treatment despite advances in tumor biology and the development of new cancer therapeutic strategies. It has been reported that these characteristics of pancreatic cancer originate from cancer stem cells within the tumor mass. It has also been reported that Fentanyl is a fast-acting analgesic that binds to the mu-opioid receptors and some other mu-opioid receptors are involved in this cancer process. In this study, we determined the effect of Fentanyl on PANC-1 cells, by assessing the gene expression of cancer stem cell marker genes (Nanog, Oct4, and Sox2) and apoptosis-related genes (BAD, Bax, Bcl-2, and p53) by Quantitative RealTime PCR. The number of cancer stem cells was determined by Flow Cytometry. The results of our study showed that Fentanyl administration decreased the number of cancer and cancer stem cells in the PANC-1 cell population, decreased the gene expression of stem cell marker and increased the expression of apoptosis-related genes. These results indicate that Fentanyl, which is used routinely in the pain palliation of pancreatic cancer, can be considered as an option in the treatment of pancreatic cancer.

Keywords

Apoptosis Cancer stem cell Fentanyl PANC-1 cell.

Celik, F., & Duran, T. (2019). Effects of Fentanyl on pancreatic cancer cell proliferation and cancer stem cell differentiation. Cellular and Molecular Biology, 65(7), 21–25. https://doi.org/10.14715/cmb/2019.65.7.5

Download Citation

References

Chand S, O'Hayer K, Blanco FF, Winter JM, Brody JR. The landscape of pancreatic cancer therapeutic resistance mechanisms. Int J Biol Sci 2016; 12:273-82.
Sellam F, Harir N, Khaled MB, Mrabent NM, Salah R, Benchouk A, et al. Delayed diagnosis of pancreatic cancer reported as more common in a population of North African young adults. J Gastrointest Oncol 2015; 6:505-10.
Fung S, Forte T, Rahal R, Niu J, Bryant H. Provincial rates and time trends in pancreatic cancer outcomes. Curr Oncol 2013; 20:279-81.
Ercan G, Karlitepe A, Ozpolat B. Pancreatic cancer stem cells and therapeutic approaches. Anticancer Res 2017; 37:2761-75.
Prieto-Vila M, Takahashi RU, Usuba W, Kohama I, Ochiya T. Drug resistance driven by cancer stem cells and their niche. Int J Mol Sci 2017; 18:E2574.
Long J, Zhang Y, Yu X, Yang J, LeBrun DG, Chen C, et al. Overcoming drug resistance in pancreatic cancer. Expert Opin Ther Targets 2011; 15:817-28.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105-11.
Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007; 1:555-67.
Subramaniam D, Ramalingam S, Houchen CW, Anant S. Cancer stem cells: a novel paradigm for cancer prevention and treatment. Mini Rev Med Chem 2010; 10:359-71.
Perusina Lanfranca M, Thompson JK, Bednar F, Halbrook C, Lyssiotis C, Levi B, et al. Metabolism and epigenetics of pancreatic cancer stem cells. Semin Cancer Biol 2018; pii:S1044-579X(18)30116-0.
Shah AN, Summy JM, Zhang J, Park SI, Parikh NU, Gallick GE. Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol 2007; 14:3629-37.
Bao B, Azmi AS, Aboukameel A, Ahmad A, Bolling-Fischer A, Sethi S, et al. Pancreatic cancer stem-like cells display aggressive behavior mediated via activation of FoxQ1. J Biol Chem 2014; 289:14520-33.
Suzuki S, Okada M, Shibuya K, Seino M, Sato A, Takeda H, et al. JNK suppression of chemotherapeutic agents-induced ROS confers chemoresistance on pancreatic cancer stem cells. Oncotarget 2015; 6:458-70.
Rauck RL, Tark M, Reyes E, Hayes TG, Bartkowiak AJ, Hassman D, et al. Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain. Curr Med Res Opin 2009; 25:2877-85.
Kress HG, OroÅ„ska A, Kaczmarek Z, Kaasa S, Colberg T, Nolte T. Efficacy and tolerability of intranasal fentanyl spray 50 to 200 mg for breakthrough pain in patients with cancer: a phase III, multinational, randomized, double-blind, placebo-controlled, crossover trial with a 10 month, open-label extenson treatment period. Clin Ther 2009; 31:1177-91.
Uomo I. Pain in pancreatic cancer: does drug treatment still play a role? JOP 2011; 12:435-7.
Sarkar FH, Li Y, Wang Z, Kong D. Pancreatic cancer stem cells and EMT in drug resistance and metastasis. Minerva Chir 2009; 64:489-500.
Kim E, Clark AL, Kiss A, Hahn JW, Wesselschmidt R, Coscia CJ, et al. Mu- and kappa-opioids induce the differantiation of embryonic stem cells to neural progenitors. J Biol Chem 2006; 281:33749-60.
Yamamizu K, Furuta S, Katayama S, Narita M, Kuzumaki N, Imai S, et al. The Îº opioid system regulates endothelial cell differentiation and pathfinding in vascular development. Blood 2011; 118:775-85.
Hanks GW, Conno F, Cherny N, Hanna M, Kalso E, McQuay HJ, et al. Morphine and alternative opioids in cancer pain: the EAPC recommendations. Br J Cancer 2001; 84:587-93.
Kocak N, Ozen F, Yildirim IH, Duran Y. Fentanyl inhibits tumorigenesis from human breast stem cells by inducing apoptosis. Asian Pac J Cancer Prev 2017; 18:735-9.
Sabir H, Dingley J, Scull-Brown E, Chakkarapani E, Thoresen M. Fentanyl induces cerebellar internal granular cell layer apoptosis in healthy newborn pigs. Front Neurol 2018; 9:294.
Wang N, Zhang Z, Lv J. Fentanyl inhibits proliferation and invasion via enhancing miR-302b expression in esophageal squamous cell carcinoma. Oncol Lett 2018; 16:459-66.

References

Chand S, O'Hayer K, Blanco FF, Winter JM, Brody JR. The landscape of pancreatic cancer therapeutic resistance mechanisms. Int J Biol Sci 2016; 12:273-82.

Sellam F, Harir N, Khaled MB, Mrabent NM, Salah R, Benchouk A, et al. Delayed diagnosis of pancreatic cancer reported as more common in a population of North African young adults. J Gastrointest Oncol 2015; 6:505-10.

Fung S, Forte T, Rahal R, Niu J, Bryant H. Provincial rates and time trends in pancreatic cancer outcomes. Curr Oncol 2013; 20:279-81.

Ercan G, Karlitepe A, Ozpolat B. Pancreatic cancer stem cells and therapeutic approaches. Anticancer Res 2017; 37:2761-75.

Prieto-Vila M, Takahashi RU, Usuba W, Kohama I, Ochiya T. Drug resistance driven by cancer stem cells and their niche. Int J Mol Sci 2017; 18:E2574.

Long J, Zhang Y, Yu X, Yang J, LeBrun DG, Chen C, et al. Overcoming drug resistance in pancreatic cancer. Expert Opin Ther Targets 2011; 15:817-28.

Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105-11.

Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007; 1:555-67.

Subramaniam D, Ramalingam S, Houchen CW, Anant S. Cancer stem cells: a novel paradigm for cancer prevention and treatment. Mini Rev Med Chem 2010; 10:359-71.

Perusina Lanfranca M, Thompson JK, Bednar F, Halbrook C, Lyssiotis C, Levi B, et al. Metabolism and epigenetics of pancreatic cancer stem cells. Semin Cancer Biol 2018; pii:S1044-579X(18)30116-0.

Shah AN, Summy JM, Zhang J, Park SI, Parikh NU, Gallick GE. Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol 2007; 14:3629-37.

Bao B, Azmi AS, Aboukameel A, Ahmad A, Bolling-Fischer A, Sethi S, et al. Pancreatic cancer stem-like cells display aggressive behavior mediated via activation of FoxQ1. J Biol Chem 2014; 289:14520-33.

Suzuki S, Okada M, Shibuya K, Seino M, Sato A, Takeda H, et al. JNK suppression of chemotherapeutic agents-induced ROS confers chemoresistance on pancreatic cancer stem cells. Oncotarget 2015; 6:458-70.

Rauck RL, Tark M, Reyes E, Hayes TG, Bartkowiak AJ, Hassman D, et al. Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain. Curr Med Res Opin 2009; 25:2877-85.

Kress HG, OroÅ„ska A, Kaczmarek Z, Kaasa S, Colberg T, Nolte T. Efficacy and tolerability of intranasal fentanyl spray 50 to 200 mg for breakthrough pain in patients with cancer: a phase III, multinational, randomized, double-blind, placebo-controlled, crossover trial with a 10 month, open-label extenson treatment period. Clin Ther 2009; 31:1177-91.

Uomo I. Pain in pancreatic cancer: does drug treatment still play a role? JOP 2011; 12:435-7.

Sarkar FH, Li Y, Wang Z, Kong D. Pancreatic cancer stem cells and EMT in drug resistance and metastasis. Minerva Chir 2009; 64:489-500.

Kim E, Clark AL, Kiss A, Hahn JW, Wesselschmidt R, Coscia CJ, et al. Mu- and kappa-opioids induce the differantiation of embryonic stem cells to neural progenitors. J Biol Chem 2006; 281:33749-60.

Yamamizu K, Furuta S, Katayama S, Narita M, Kuzumaki N, Imai S, et al. The Îº opioid system regulates endothelial cell differentiation and pathfinding in vascular development. Blood 2011; 118:775-85.

Hanks GW, Conno F, Cherny N, Hanna M, Kalso E, McQuay HJ, et al. Morphine and alternative opioids in cancer pain: the EAPC recommendations. Br J Cancer 2001; 84:587-93.

Kocak N, Ozen F, Yildirim IH, Duran Y. Fentanyl inhibits tumorigenesis from human breast stem cells by inducing apoptosis. Asian Pac J Cancer Prev 2017; 18:735-9.

Sabir H, Dingley J, Scull-Brown E, Chakkarapani E, Thoresen M. Fentanyl induces cerebellar internal granular cell layer apoptosis in healthy newborn pigs. Front Neurol 2018; 9:294.

Wang N, Zhang Z, Lv J. Fentanyl inhibits proliferation and invasion via enhancing miR-302b expression in esophageal squamous cell carcinoma. Oncol Lett 2018; 16:459-66.

Author biographies is not available.