Premium
Aneustat (OMN54) has aerobic glycolysis‐inhibitory activity and also immunomodulatory activity as indicated by a first‐generation PDX prostate cancer model
Author(s) -
Qu Sifeng,
Xue Hui,
Dong Xin,
Lin Dong,
Wu Rebecca,
Nabavi Noushin,
Collins Colin C.,
Gleave Martin E.,
Gout Peter W.,
Wang Yuzhuo
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31310
Subject(s) - lncap , immune system , prostate cancer , cancer research , immunosuppression , anaerobic glycolysis , cancer , cancer cell , cytotoxic t cell , glycolysis , cd8 , tumor microenvironment , immunology , medicine , biology , in vitro , metabolism , biochemistry
Aneustat (OMN54) is a multivalent, botanical anticancer candidate therapeutic. A recent Phase‐I clinical trial has indicated that it is well tolerated by patients and has immunomodulatory activity. In our study, using in vitro and in vivo prostate cancer models, we investigated Aneustat with regard to effects on (i) cancer‐generated immunosuppression based on aerobic glycolysis leading to acidification of the tumor microenvironment, and (ii) immune‐related processes such as macrophage differentiation and shifts in the intratumoral levels of host immune cells. Aneustat markedly reduced glucose consumption, lactic acid secretion, glycolysis‐related gene expressions and proliferation of human LNCaP prostate cancer cells. In addition, Aneustat induced differentiation of RAW264.7 macrophages to the M1 anticancer phenotype. Treatment of LNCaP xenografts and first‐generation patient‐derived prostate cancer tissue xenografts with Aneustat in both cases led to a marked shift in intratumoral host (mouse/patient) immune cell levels: a higher ratio of cytotoxic CD8 + T/Treg cells, higher numbers of NK cells, lower numbers of Treg cells and MDSCs, i.e. changes favoring the host anticancer immune response. Taken together, the data indicate that Aneustat has immunomodulatory activity based on inhibition of aerobic glycolysis which in patients may lead to reduction of cancer‐induced immunosuppression. Furthermore, first‐generation patient‐derived cancer tissue xenograft models may be used for screening compounds for immunomodulatory activity.