PMID- 32361165 OWN - NLM STAT- MEDLINE DCOM- 20210211 LR - 20210211 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 127 DP - 2020 Jul TI - Water extract from Euglena gracilis prevents lung carcinoma growth in mice by attenuation of the myeloid-derived cell population. PG - 110166 LID - S0753-3322(20)30358-9 [pii] LID - 10.1016/j.biopha.2020.110166 [doi] AB - The partially purified water extract from Euglena gracilis (EWE) was evaluated for its antitumor and immunomodulatory effects in cell cultures and in a mouse orthotopic lung carcinoma allograft model. In two-dimensional cell culture, the EWE treatment inhibited cell growth of both murine Lewis lung carcinoma (LLC) and human lung carcinoma cells (A549 and H1299) in a dose- and time-dependent manner. In contrast, the growth of mouse bone marrow cells (BMCs), but not mouse splenocytes (SPLs), was stimulated by the treatment with EWE. In three-dimensional spheroid culture, spheroid growth of LLC cells was significantly attenuated by EWE treatment. In a mouse LLC orthotopic allograft model, pretreatment with EWE (150-200 mg/kg/day, via drinking water) three weeks prior to the LLC cell inoculation, but not post-treatment after LLC cell inoculation, significantly attenuated the growth of LLC tumors in immunocompetent syngeneic mouse lung. This tumor growth attenuation coincided with a significant decrease in the population of myeloid-derived cells, primarily neutrophils. Flow cytometric analysis revealed that the EWE treatment significantly attenuated growth of granulocytic myeloid-derived suppressor cells (gMDSC) in BMCs and that this decrease was due to induction of gMDSC-specific apoptosis and differentiation of monocytic MDSCs (mMDSC) to macrophages. The present study provides evidence that EWE pretreatment inhibits lung carcinoma growth mainly by stimulating host antitumor immunity through attenuation of growth of gMDSCs and decreasing the number of peripheral granulocytes. This study suggests that the partially purified extract derived from Euglena gracilis contains significant bioactive materials that prevent lung carcinoma growth. CI - Copyright (c) 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved. FAU - Ishiguro, Susumu AU - Ishiguro S AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: isusumu@vet.ksu.edu. FAU - Upreti, Deepa AU - Upreti D AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: deepa07@vet.ksu.edu. FAU - Robben, Nicole AU - Robben N AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: ndrobben@ksu.edu. FAU - Burghart, Riley AU - Burghart R AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: rireann@ksu.edu. FAU - Loyd, Mayme AU - Loyd M AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: mkloyd@ksu.edu. FAU - Ogun, Damilola AU - Ogun D AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: dogun@vet.ksu.edu. FAU - Le, Tran AU - Le T AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: tle12@vet.ksu.edu. FAU - Delzeit, Jennifer AU - Delzeit J AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: jenny7@k-state.edu. FAU - Nakashima, Arashi AU - Nakashima A AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: aarashi@ksu.edu. FAU - Thakkar, Ravindra AU - Thakkar R AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: ravithakkar@vet.ksu.edu. FAU - Nakashima, Ayaka AU - Nakashima A AD - Euglena Co., Ltd., Minato-ku, Tokyo 108-0014, Japan. Electronic address: nakashima@euglena.jp. FAU - Suzuki, Kengo AU - Suzuki K AD - Euglena Co., Ltd., Minato-ku, Tokyo 108-0014, Japan. Electronic address: suzuki@euglena.jp. FAU - Comer, Jeffrey AU - Comer J AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: jeffcomer@ksu.edu. FAU - Tamura, Masaaki AU - Tamura M AD - Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, United States. Electronic address: mtamura@vet.ksu.edu. LA - eng PT - Journal Article DEP - 20200428 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Antineoplastic Agents) RN - 0 (Immunologic Factors) RN - 059QF0KO0R (Water) SB - IM MH - A549 Cells MH - Animals MH - Antineoplastic Agents/administration & dosage/isolation & purification/*pharmacology MH - Apoptosis/drug effects MH - Bone Marrow Cells/drug effects/metabolism MH - Carcinoma, Lewis Lung/*drug therapy/pathology MH - Cell Differentiation/drug effects MH - Cell Line, Tumor MH - Dose-Response Relationship, Drug MH - Euglena gracilis/*metabolism MH - Female MH - Granulocytes/drug effects/metabolism MH - Humans MH - Immunologic Factors/administration & dosage/isolation & purification/pharmacology MH - Lung Neoplasms/*drug therapy/pathology MH - Mice MH - Mice, Inbred C57BL MH - Myeloid-Derived Suppressor Cells/metabolism MH - Time Factors MH - Water/chemistry OTO - NOTNLM OT - Apoptosis OT - Cancer cell growth inhibition OT - Inhibition of MDSC OT - Inhibition of pro-tumorigenic immunity OT - Lung cancer OT - Water extract from Euglena gracilis EDAT- 2020/05/04 06:00 MHDA- 2021/02/12 06:00 CRDT- 2020/05/04 06:00 PHST- 2020/01/22 00:00 [received] PHST- 2020/04/10 00:00 [revised] PHST- 2020/04/13 00:00 [accepted] PHST- 2020/05/04 06:00 [pubmed] PHST- 2021/02/12 06:00 [medline] PHST- 2020/05/04 06:00 [entrez] AID - S0753-3322(20)30358-9 [pii] AID - 10.1016/j.biopha.2020.110166 [doi] PST - ppublish SO - Biomed Pharmacother. 2020 Jul;127:110166. doi: 10.1016/j.biopha.2020.110166. Epub 2020 Apr 28.