Hemidesmus indicus induces immunogenic death in human colorectal cancer cells

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.

Immune system activation by natural products and complex fractions: a network pharmacology approach in cancer treatment

“…Complex fractions can have immunomodulatory capacities and antitumor activity as indicated recently by Turrini et al, who showed that a decoction from plant roots of Hemidesmus indicus is able to induce ER stress along with the hallmarks of ICD to stimulate DC maturation and the upregulation of CD83 as a costimulatory signal [40]. Moreover, P2Et, a gallotannin-rich fraction extracted from the red fruits of Caesalpinia spinosa, was initially reported for its DC maturation after ICD induction [40] cytotoxic properties on several cancer cell lines [41]. P2Et has been previously characterized as a complex polyphenol-rich fraction with antitumoral activity and was shown to contain a large amount of gallic acid after acid hydrolysis, mainly due to the presence of gallic acid derivatives like galloyl quinic acids.…”

Medicinal plants commonly used against cancer in traditional medicine formulae in Sri Lanka

“…Hemidesmus indicus (Apocynaceae), commonly known as Indian sarsaparilla or "iramusu" in Sinhalese and "nannari" in Tamil, is used in poly-herbal preparations aimed against cancer; the root is mostly used in traditional medicine preparations (Turrini et al, 2018). The leaves are used to make gruel or herbal drinks in Sri Lanka.…”

“…A decoction of Hemidesmus indicus was shown to induce an immunogenic type of cell death in DLD1 (colon cancer) cells, stimulating an upregulation of CD83 that caused dendritic cell maturation. Thus, this plant has the potential to act as an adjuvant agent by enhancing an immunogenic response in cancer (Turrini et al, 2018). In other studies, a poly-herbal formulation of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes induced apoptosis in HepG2 cells through activation of caspases 3 and 9 (Ira Thabrew et al, 2005, Samarakoon et al, 2012).…”

Hemidesmus indicus induces apoptosis via proteasome inhibition and generation of reactive oxygen species

“…As an example, the root decoction of HI is able to prompt all in vitro hallmarks of a particular type of cell death, i.e. the immunogenic cell death 11 , which activates dendritic cells to promote antitumor immunity 12 . A clinically relevant evidence is that it exhibits cytotoxic effect in blasts from acute myeloid leukemic patients and potentiates the cytotoxicity of widely used anticancer drugs 13 .…”