Treatment of Hematological Malignancies with Glycyrrhizic Acid

Hostetler, Bryan; Uchakina, Olga N.; Ban, Hao; McKallip, Robert J.

doi:10.21873/anticanres.11409

Cited by 15 publications

(8 citation statements)

References 20 publications

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“…OOS is a nutritional supplement which contains several natural products, some of them with proven antioxidant and antitumoral properties [10,11,12,14,28,29,30]. Because of the characteristics of such products, including their ample therapeutic index, their use is safe and may offer therapeutic value associated with the antitumoral properties of several of its constituting compounds.…”

Section: Discussionmentioning

confidence: 99%

Central Role of Cell Cycle Regulation in the Antitumoral Action of Ocoxin

et al. 2019

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Nutritional supplements which include natural antitumoral compounds could represent safe and efficient additives for cancer patients. One such nutritional supplement, Ocoxin Oral solution (OOS), is a composite formulation that contains several antioxidants and exhibits antitumoral properties in several in vitro and in vivo tumor conditions. Here, we performed a functional genomic analysis to uncover the mechanism of the antitumoral action of OOS. Using in vivo models of acute myelogenous leukemia (AML, HEL cells, representative of a liquid tumor) and small-cell lung cancer (GLC-8, representative of a solid tumor), we showed that OOS treatment altered the transcriptome of xenografted tumors created by subcutaneously implanting these cells. Functional transcriptomic studies pointed to a cell cycle deregulation after OOS treatment. The main pathway responsible for this deregulation was the E2F–TFDP route, which was affected at different points. The alterations ultimately led to a decrease in pathway activation. Moreover, when OOS-deregulated genes in the AML context were analyzed in patient samples, a clear correlation with their levels and prognosis was observed. Together, these data led us to suggest that the antitumoral effect of OOS is due to blockade of cell cycle progression mainly caused by the action of OOS on the E2F–TFDP pathway.

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Section: Discussionmentioning

confidence: 99%

Central Role of Cell Cycle Regulation in the Antitumoral Action of Ocoxin

et al. 2019

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“…Viability of K562 cells (human chronic myeloid leukemia) was reduced by GA treatment at concentration higher than 2.0 mM. Combination of GA and anti-leukemic drug imatinib in the ratio 2 mM GA per 0.4 μM imatinib resulted in two fold increase of DNA fragmentation in K562 cell culture compared with caused by 2.0 mM GA or 0.4 μM imatinib alone (Hostetler et al, 2017).…”

Section: Anticancer Activitymentioning

confidence: 97%

Glycyrrhizic acid as a multifunctional drug carrier – From physicochemical properties to biomedical applications: A modern insight on the ancient drug

Selyutina

Polyakov

2019

International Journal of Pharmaceutics

152

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A B S T R A C TGlycyrrhizic acid is the main active component of Licorice root which has been known in traditional Chinese and Japanese medicine since ancient times. In these cultures glycyrrhizic acid (GA) is one of the most frequently used drugs. However, only in 21-st century a novel unusual property of the GA to enhance the activity of other drugs has been discovered. The review describes briefly the experimental evidences of wide spectrum of own biological activities of glycyrrhizic acid as well as discusses the possible mechanisms of the ability of GA to enhance the activity of other drugs. We have shown that due to its amphiphilic nature GA is able to form self-associates in aqueous and non-aqueous media, as well as water soluble complexes with a wide range of lipophilic drugs. The main purpose of our review is to focus reader's attention on physicochemical studies of the molecular mechanisms of GA activity as a drug delivery system (DDS). In our opinion, the most intriguing feature of glycyrrhizic acid which might be the key factor in its therapeutic activity is the ability of GA to incorporate into the lipid bilayer and to increase the membrane fluidity and permeability. The ability of biomolecules and their aggregates to change the properties of cell membranes is of great significance, from both fundamental and practical points of view. monstrated the ability of GA to interact with cell membrane and to https://doi.

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“…For the past two decades, glycyrrhizic acid has been used clinically in China and Japan, with satisfactory therapeutic effects [98]. It has been confirmed to be safe and non-toxic [99], and it has inhibitory effects on many cancers, including leukemia, gliomas, colon cancer, and lung cancer [100–111]. Here we show that glycyrrhizic acid has inhibitory effects on EBV-transformed LCLs, which mimic EBV-associated lymphoproliferative diseases.…”

Section: Discussionmentioning

confidence: 60%

Using glycyrrhizic acid to target sumoylation processes during Epstein-Barr virus latency

et al. 2019

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Cellular sumoylation processes are proposed targets for anti-viral and anti-cancer therapies. We reported that Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) dysregulates cellular sumoylation processes, contributing to its oncogenic potential in EBV-associated malignancies. Ginkgolic acid and anacardic acid, known inhibitors of sumoylation, inhibit LMP1-induced protein sumoylation; however, both drugs have adverse effects in hosts. Here we test the effects of glycyrrhizic acid, a medicinal botanical extract with anti-inflammatory, anti-carcinogenic, and anti-viral properties, on cellular sumoylation processes. While glycyrrhizic acid is known to inhibit EBV penetration, its affect on cellular sumoylation processes remains to be documented. We hypothesized that glycyrrhizic acid inhibits cellular sumoylation processes and may be a viable treatment for Epstein-Barr virus-associated malignancies. Results showed that glycyrrhizic acid inhibited sumoylation processes (without affecting ubiquitination processes), limited cell growth, and induced apoptosis in multiple cell lines. Similar to ginkgolic acid; glycyrrhizic acid targeted the first step of the sumoylation process and resulted in low levels of spontaneous EBV reactivation. Glycyrrhizic acid did not affect induced reactivation of the virus, but the presence of the extract did reduce the ability of the produced virus to infect additional cells. Therefore, we propose that glycyrrhizic acid may be a potential therapeutic drug to augment the treatment of EBV-associated lymphoid malignancies.

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Treatment of Hematological Malignancies with Glycyrrhizic Acid

Cited by 15 publications

References 20 publications

Central Role of Cell Cycle Regulation in the Antitumoral Action of Ocoxin

Central Role of Cell Cycle Regulation in the Antitumoral Action of Ocoxin

Glycyrrhizic acid as a multifunctional drug carrier – From physicochemical properties to biomedical applications: A modern insight on the ancient drug

Using glycyrrhizic acid to target sumoylation processes during Epstein-Barr virus latency

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