Hemidesmus indicus induces immunogenic death in human colorectal cancer cells.

Eleonora Turrini,Patrizia Hrelia,Fabiana Morroni,Massimo Tacchini,Valeria Governa,Elena Catanzaro,Carmela Fimognari,Giulia Sita,Cinzia Calcabrini,Emanuele Trella,Manuele G Muraro,Valentina Mele

doi:10.18632/oncotarget.25325

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.

Highlights

According to the FDA guidelines, a botanical drug is set up from a botanical drug substance and is proposed for use as a drug
As immunogenic cell death (ICD) is a particular form of apoptotic cell death, we investigated the cell death modalities that were engaged in response to H.i
To confirm that the observed sub-G1 peak was due to apoptosis, we analyzed the expression of 85 kDa fragment of cleaved poly ADP-ribose polymerase (PARP), an important reporter for caspase 3 activation

Summary

Introduction

According to the FDA guidelines, a botanical drug is set up from a botanical drug substance and is proposed for use as a drug. A botanical drug, by definition, is made out of multiple compounds [1]. Such complex composition may give advantages, in managing complex diseases with polymorphic nature that cannot respond to the standard single drugs. A gallotannin-rich standardized fraction from Caesalpinia spinosa is endowed with immune system dependent-anticancer activity. It induces immunogenic cell death (ICD), dendritic cells (DCs) activation, and increased generation of melanoma associated antigen-specific T cells [4]

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Conclusion