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Lv. J Transl Genet Genom 2021;5:414-22 https://dx.doi.org/10.20517/jtgg.2021.34 Page 418

Figure 1. (A) Cellular outcome of HMGB1 interactions with receptors. (B) Hypothetical mode of action of HMGB1 inhibitors.

HMGB1 by antibody was also confirmed to effectively suppress the tumor progression in malignant
mesothelioma in vitro and in vivo . In summary, these studies proved the curative utility of anti-HMGB1
[73]
antibody for cancer treatment generally, which may also be applied for PCa treatment.

The utilization of naturally occurring compounds such as glycyrrhizin, glycyrrhetinic acid, ethyl pyruvate,
and green tea phenols, especially (-)-epigallocatechin-3-gallate [Figure 1B], may be another promising
approach for HMGB1 targeted therapy, as all of these products have been proved to work against HMGB1
in various cell/disease models [54,74,75] . Specifically, Shetty et al. demonstrated that 18-alpha glycyrrhetinic
[54]
acid, a derivative of glycyrrhizin that is sufficiently expressed in the licorice root, can reduce the expression
of HMGB1 and lead to the curative effects in PCa cells. Other natural compounds known to target HMGB1
[77]
[78]
include some cholinergic agonists , thrombomodulin , and low molecular-weight heparin . All these
[76]
natural agents could be tested in PCa patients who show high levels of HMGB1.