Abstract 4706: Extracellular polysaccharides extracted from <i>Parachlorella kessleri</i> enhance host antitumor immune responses and inhibit colon carcinoma growth in mice
Authors: Susumu Ishiguro, Deepthi Uppalapati, Zachary Goldsmith, Dana Robertson, Jacob Hodge, Hayley Holt, Arashi Nakashima, Katie Turner, Masaaki Tamura
Journal: Cancer Research (2018)

Abstract Natural products obtained from various resources are often found to be new sources of effective drugs for disease including cancer. The novel extracellular polysaccharides (exopolysaccharides) purified from Parachlorella kessleri (PCEPS), a generous gift by Panac ADVANCE Co. Ltd. (Tokyo, Japan), 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 cell proliferation 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 T lymphoblasts), but not THP-1 human monocytes/macrophages, was significantly attenuated by PCEPS treatment. In transwell co-culture of CT26 and HL-60, THP-1 or Jurkat cells, mRNA level of NOX2 in HL-60 and THP-1 cells, and TNFα, IFNγ, IL-2 and granzyme B (GZMB) in Jurkat cells was significantly increased by PCEPS treatment. In a mouse CT26 colon carcinoma peritoneal dissemination model, intraperitoneal injection of PCEPS (10 mg/kg, started from 1 week after CT26 inoculation for 11 days, twice per week) significantly attenuated the growth of CT26 colon carcinoma in syngeneic mice by PCEPS treatment-associated apoptosis without any noticeable adverse effect. Analysis of subpopulation of intraperitoneally infiltrating immune cells collected from CT26 cell tumor-bearing mice found that PCEPS treatment increased CD4+ and CD8+ T lymphocytes, CD19+ B cell, and CD68+ macrophage populations. In contrast, 33D1+ dendritic cell and LY6G+ neutrophil populations were decreased as compared to PBS-treated group. 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. This study was supported by Kansas State University Johnson Cancer Research Center 2011JCRC-EQ (MT), 2014CRA (ZG and MT), 2015CRA (JH, HH, AN, and MT), 2016CRA (HH and MT), College of Veterinary Medicine Dean's funds 2010CVM-EQ (MT), and NIH grant P20 RR017686 (MT). Citation Format: Susumu Ishiguro, Deepthi Uppalapati, Zachary Goldsmith, Dana Robertson, Jacob Hodge, Hayley Holt, Arashi Nakashima, Katie Turner, Masaaki Tamura. Extracellular polysaccharides extracted from Parachlorella kessleri enhance host antitumor immune responses and inhibit colon carcinoma growth in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4706.