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1.
Biomed Pharmacother ; 127: 110166, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32361165

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Lewis Lung/drug therapy , Euglena gracilis/metabolism , Lung Neoplasms/drug therapy , A549 Cells , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/isolation & purification , Apoptosis/drug effects , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Carcinoma, Lewis Lung/pathology , Cell Differentiation/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , Female , Granulocytes/drug effects , Granulocytes/metabolism , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/isolation & purification , Immunologic Factors/pharmacology , Lung Neoplasms/pathology , Mice , Mice, Inbred C57BL , Myeloid-Derived Suppressor Cells/metabolism , Time Factors , Water/chemistry
2.
PLoS One ; 12(4): e0175064, 2017.
Article in English | MEDLINE | ID: mdl-28380056

ABSTRACT

The newly purified extracellular polysaccharides (exopolysaccharides) from Parachlorella kessleri (PCEPS) were evaluated on their antitumor and immunomodulatory effects in cell culture and mouse colon carcinoma peritoneal dissemination model. In two-dimensional cell culture, the PCEPS treatment inhibited cell growth of both murine and human colon carcinoma cells in a dose- and time-dependent manner. In contrast, the growth of mouse splenocytes (SPLs) and bone marrow cells (BMCs) were stimulated by the treatment with PCEPS. The treatment with PCEPS also increased specific subpopulations of the cells in BMCs: antigen presenting cells (CD19+ B cells, 33D1+ dendritic cells and CD68+ macrophage) and CD8+ cytotoxic T cells. In three-dimensional spheroid culture, spheroid growth of CT26 cells co-cultured with HL-60 human neutrophilic promyeloblasts and Jurkat cells (human lymphoblasts), but not THP-1 human monocyte/macrophage was significantly attenuated by PCEPS treatment. In a mouse CT26 colon carcinoma peritoneal dissemination model, intraperitoneal injection of PCEPS (10 mg/kg, twice per week) significantly attenuated the growth of CT26 colon carcinoma in syngeneic mice. The present study suggests that PCEPS inhibits colon carcinoma growth via direct cell growth inhibition and a stimulation of the host antitumor immune responses. Taken together, the current study suggests that exopolysaccharides derived from Parachlorella kessleri contain significant bioactive materials that inhibit colon carcinoma growth.


Subject(s)
Antineoplastic Agents/therapeutic use , Chlorella/chemistry , Colonic Neoplasms/drug therapy , Immunologic Factors/therapeutic use , Plant Extracts/therapeutic use , Polysaccharides/therapeutic use , Animals , Bone Marrow Cells/drug effects , Cell Line, Tumor , Chlorophyta , Dose-Response Relationship, Drug , Female , Humans , Mice , Mice, Inbred BALB C , Spleen/cytology , Spleen/drug effects
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