LAUSR

Natural products obtained from various resources are often used as new compounds or seed compounds of effective drugs for disease including cancer. The water extract partially purified from the cell membrane fraction of Chlorella vulgaris (CMWE) was evaluated on its antitumor and immunomodulatory effects in cell culture and a colon carcinoma mouse model. The CMWE was filtered through 0.22 μm pore size membrane for all experiments. In two-dimensional cell cultures, the CMWE treatment inhibited cell growth of both murine and human colon carcinoma cells in a dose- and time-dependent manner. In contrast, the cell proliferation of mouse splenocytes (SPLs) and bone marrow cells (BMCs) were stimulated by the treatment with CMWE. The treatment with CMWE also increased specific subpopulations of the cells in BMCs: antigen presenting cells (CD19 + B cells, 33D1 + dendritic cells and CD68 + macrophage), CD4 + and CD8 + T cells, whereas LY-6G + neutrophils were decreased. In a three-dimensional spheroid culture, spheroid growth of CT26 cells co-cultured with Jurkat cells (human T lymphoblasts) was significantly attenuated by CMWE treatment via induction of apoptosis. In a two-dimensional cell culture of Jurkat cells, mRNA levels of TNFα, IFNγ and granzyme B were significantly increased by CMWE treatment. In a mouse CT26 colon carcinoma peritoneal dissemination model, intraperitoneal injection of CMWE (30 mg/kg/day, started from 3 days after CT26 inoculation for 9 days, every other day) significantly attenuated the growth of CT26 colon carcinoma nodules in syngeneic mice by CMWE treatment-associated apoptosis without any noticeable adverse effect. Analysis of subpopulation of intraperitoneally infiltrating immune cells collected from CT26 cell tumor-bearing mice, indicated that CMWE treatment increased CD4 + and CD8 + T lymphocytes, CD19 + B cell, and CD68 + macrophage populations. In contrast, LY6G + neutrophil population was decreased as compared to PBS-treated group. The present study suggests that CMWE 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 water extract obtained from the cell membrane fraction of Chlorella vulgaris contain significant bioactive materials that inhibit colon carcinoma growth. This study was supported by 2016EUGLENA-RC1 (MT), 2017EUGLENA-RC2 (MT), Kansas State University Johnson Cancer Research Center 2018CRA (NR and MT), and NIH grant P20 RR017686 (MT). Citation Format: Susumu Ishiguro, Nicole Robben, Deepa Upreti, Paige Cote, Sarah Greenway, Riley Burghart, Ayaka Nakashima, Masaaki Tamura. Water extract from Chlorella vulgaris cell membrane fraction enhances host antitumor immune responses and inhibit colon carcinoma growth in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4144.