Hemidesmus indicus induces immunogenic death in human colorectal cancer cells

// Eleonora Turrini 1, * , Elena Catanzaro 1, * , Manuele G. Muraro 2, * , Valeria Governa 3 , Emanuele Trella 2 , Valentina Mele 3 , Cinzia Calcabrini 1 , Fabiana Morroni 4 , Giulia Sita 4 , Patrizia Hrelia 4 , Massimo Tacchini 5 and Carmela Fimognari 1 1 Department for Life Quality Studies, Alma Mater Studiorum–University of Bologna, Rimini, Italy 2 Oncology Surgery, Department of Biomedicine, University Hospital of Basel and University of Basel, ZLF, Basel-Switzerland 3 Cancer Immunotherapy, Department of Biomedicine, University Hospital of Basel and University of Basel, ZLF, Basel-Switzerland 4 Department of Pharmacy and Biotechnology, Alma Mater Studiorum–University of Bologna, Bologna, Italy 5 Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy * These authors contributed equally to this work Correspondence to: Carmela Fimognari, email: carmela.fimognari@unibo.it Keywords: Hemidesmus indicus; immunogenic cell death; adjuvant activity; botanical drugs; colorectal cancer Received: July 29, 2017      Accepted: April 16, 2018      Published: May 11, 2018 ABSTRACT The ability of anticancer treatments to promote the activation of tumor-reactive adaptive immune responses is emerging as a critical requirement underlying their clinical effectiveness. We investigated the ability of Hemidesmus indicus , a promising anticancer botanical drug, to stimulate immunogenic cell death in a human colorectal cancer cell line (DLD1). Here we show that Hemidesmus treatment induces tumor cell cytotoxicity characterized by surface expression of calreticulin, increased HSP70 expression and release of ATP and HMGB1. Remarkably, the exposure to released ICD-inducer factors from Hemidesmus -treated DLD1 cells caused a modest induction of CD14-derived dendritic cells maturation, as demonstrated by the increased expression of CD83. Moreover, at sub-toxic concentrations, H.i. treatment of monocytes and dendritic cells induced their mild activation, suggesting its additional direct immunostimulatory activity. These data indicate that Hemidesmus indicus induces immunogenic cell death in human tumor cells and suggest its potential relevance in innovative cancer immunotherapy protocols.