Enzyme-treated Asparagus Extract Down-regulates Heat Shock Protein 27 of Pancreatic Cancer Cells

Overview

Journal In Vivo

Specialty Oncology

Date 2018 Jun 25

PMID 29936456

Citations 4

Authors

Takuya Shimada

Yuta Nanimoto

Byron Baron

Takao Kitagawa

Kazuhiro Tokuda

Yasuhiro Kuramitsu

Affiliations

Soon will be listed here.

Abstract

Background/aim: From the standpoint of cancer therapy, it is valuable to enhance the anticancer effects of chemotherapy. Our previous reports revealed that up-regulation of heat-shock protein 27 (HSP27) has been linked to gemcitabine resistance of pancreatic cancer cells. Enzyme-treated asparagus extract (ETAS) is an extract that is produced from asparagus. The purpose of this study was to investigate the effect of ETAS on the expression of HSP27 and other HSPs in the gemcitabine-resistant pancreatic cancer cell line KLM1-R.

Materials And Methods: KLM1-R cells were treated with ETAS, and expression levels of HSPs, including HSP27, were investigated by western blotting.

Results: ETAS down-regulated HSP27 and pHSP27 (serine 78) in KLM1-R cells, but, HSP70 and GRP78 levels were not altered.

Conclusion: This study suggests the potential therapeutic benefit of ETAS in enhancing anticancer effects by its combination with gemcitabine for patients with pancreatic cancer.

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References

Ueno H, Ikeda M, Ueno M, Mizuno N, Ioka T, Omuro Y . Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Cancer Chemother Pharmacol. 2016; 77(3):595-603. DOI: 10.1007/s00280-016-2972-3. View

Kang S, Kang K, Kim K, Kwon B, Kim S, Lee H . Upregulated HSP27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability. BMC Cancer. 2008; 8:286. PMC: 2567332. DOI: 10.1186/1471-2407-8-286. View

Hirata I, Naito Y, Handa O, Hayashi N, Mizushima K, Adachi S . Heat-shock protein 70-overexpressing gastric epithelial cells are resistant to indomethacin-induced apoptosis. Digestion. 2009; 79(4):243-50. DOI: 10.1159/000215352. View

Mori-Iwamoto S, Taba K, Kuramitsu Y, Ryozawa S, Tanaka T, Maehara S . Interferon-gamma down-regulates heat shock protein 27 of pancreatic cancer cells and helps in the cytotoxic effect of gemcitabine. Pancreas. 2009; 38(2):224-6. DOI: 10.1097/MPA.0b013e3181773970. View

Sabirzhanov B, Stoica B, Hanscom M, Piao C, Faden A . Over-expression of HSP70 attenuates caspase-dependent and caspase-independent pathways and inhibits neuronal apoptosis. J Neurochem. 2012; 123(4):542-54. PMC: 3753080. DOI: 10.1111/j.1471-4159.2012.07927.x. View

Suenaga S, Kuramitsu Y, Kaino S, Maehara S, Maehara Y, Sakaida I . Active hexose-correlated compound down-regulates HSP27 of pancreatic cancer cells, and helps the cytotoxic effect of gemcitabine. Anticancer Res. 2014; 34(1):141-6. View

Daugaard M, Rohde M, Jaattela M . The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions. FEBS Lett. 2007; 581(19):3702-10. DOI: 10.1016/j.febslet.2007.05.039. View

Soo E, Ng Y, Bay B, Yip G . Heat shock proteins and neurodegenerative disorders. ScientificWorldJournal. 2008; 8:270-4. PMC: 5848761. DOI: 10.1100/tsw.2008.48. View

Liu C, Chen S, Wu M, Jao S, Lin Y, Yang C . The molecular and clinical verification of therapeutic resistance via the p38 MAPK-Hsp27 axis in lung cancer. Oncotarget. 2016; 7(12):14279-90. PMC: 4924714. DOI: 10.18632/oncotarget.7306. View

10.

Mori-Iwamoto S, Kuramitsu Y, Ryozawa S, Mikuria K, Fujimoto M, Maehara S . Proteomics finding heat shock protein 27 as a biomarker for resistance of pancreatic cancer cells to gemcitabine. Int J Oncol. 2007; 31(6):1345-50. View

11.

Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G . Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties. Cell Cycle. 2006; 5(22):2592-601. DOI: 10.4161/cc.5.22.3448. View

12.

Mori-Iwamoto S, Kuramitsu Y, Ryozawa S, Taba K, Fujimoto M, Okita K . A proteomic profiling of gemcitabine resistance in pancreatic cancer cell lines. Mol Med Rep. 2011; 1(3):429-34. View

13.

Kuramitsu Y, Wang Y, Taba K, Suenaga S, Ryozawa S, Kaino S . Heat-shock protein 27 plays the key role in gemcitabine-resistance of pancreatic cancer cells. Anticancer Res. 2012; 32(6):2295-9. View

14.

Gabai V, Yaglom J, Wang Y, Meng L, Shao H, Kim G . Anticancer Effects of Targeting Hsp70 in Tumor Stromal Cells. Cancer Res. 2016; 76(20):5926-5932. PMC: 5065765. DOI: 10.1158/0008-5472.CAN-16-0800. View

15.

Ito T, Goto K, Takanari J, Miura T, Wakame K, Nishioka H . Effects of enzyme-treated asparagus extract on heat shock protein 70, stress indices, and sleep in healthy adult men. J Nutr Sci Vitaminol (Tokyo). 2014; 60(4):283-90. DOI: 10.3177/jnsv.60.283. View

16.

Ciocca D, Calderwood S . Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005; 10(2):86-103. PMC: 1176476. DOI: 10.1379/csc-99r.1. View

17.

Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N . Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013; 31(13):1640-8. DOI: 10.1200/JCO.2012.43.3680. View

18.

SCHLESINGER M . Heat shock proteins. J Biol Chem. 1990; 265(21):12111-4. View

19.

Tokunaga M, Baron B, Kitagawa T, Tokuda K, Kuramitsu Y . Active Hexose-correlated Compound Down-regulates Heat Shock Factor 1, a Transcription Factor for HSP27, in Gemcitabine-resistant Human Pancreatic Cancer Cells. Anticancer Res. 2015; 35(11):6063-7. View

20.

Jagadish N, Parashar D, Gupta N, Agarwal S, Suri V, Kumar R . Heat shock protein 70-2 (HSP70-2) is a novel therapeutic target for colorectal cancer and is associated with tumor growth. BMC Cancer. 2016; 16:561. PMC: 4966739. DOI: 10.1186/s12885-016-2592-7. View