Dipotassium Glycyrrhizinate on Melanoma Cell Line: Inhibition of Cerebral Metastases Formation by Targeting NF-kB Genes-Mediating MicroRNA-4443 and MicroRNA-3620—Dipotassium Glycyrrhizinate Effect on Melanoma

Bonafé, Gabriel Alves; Santos, Jéssica Silva dos; Ziegler, Jussara Vaz; Marson, Fernando Augusto Lima; Rocha, Thalita; Ortega, Manoela Marques

doi:10.3390/ijms23137251

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…Furthermore, studies showed that GL inhibited the metastasis of melanoma cells by regulating T helper type 2 (Th2) cell resistance, interfering with further the dissemination of melanoma ( Kobayashi et al, 2002 ; Su et al, 2017 ). Dipotassium of GL inhibited the metastases of melanoma Cells into brain ( Bonafe et al, 2022b ).…”

Section: Roles Of Gl In Cancer Therapymentioning

confidence: 99%

Advances in the roles of glycyrrhizic acid in cancer therapy

Zhang¹,

Sheng²,

Xiao³

et al. 2023

Front. Pharmacol.

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Since the first 70 years of reporting cancer chemotherapy, malignant tumors have been the second most common cause of death in children and adults. Currently, the commonly used anti-cancer methods include surgery, chemotherapy, radiotherapy, and immunotherapy. Although these treatment methods could alleviate cancer, they lead to different forms of side effects and have no particularly significant effect on prolonging the patients’ life span. Glycyrrhizic acid (GL), a native Chinese herbal extract, has a wide range of pharmacological effects, such as anti-cancer, anti-inflammatory, antioxidant, and immune regulation. In this review, the anti-cancer effects and mechanisms of GL are summarized in various cancers. The inhibition of GL on chemotherapy-induced side effects, including hepatotoxicity, nephrotoxicity, genotoxicity, neurotoxicity and pulmonary toxicity, is highlighted. Therefore, GL may be a promising and ideal drug for cancer therapy.

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Section: Roles Of Gl In Cancer Therapymentioning

confidence: 99%

Advances in the roles of glycyrrhizic acid in cancer therapy

Zhang¹,

Sheng²,

Xiao³

et al. 2023

Front. Pharmacol.

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“…In accordance with the results observed in the present study, another recent study has suggested that DPG has an apoptotic, anti-proliferative, and anti-migratory effect on the melanoma cell line (SK-MEL-28) bearing the BRAF mutation. DPG was also able to inhibit cancer stem-like cells that may cause cerebral tumor formation ( 39 ). In addition, DPG treatment has shown that SK-MEL-28 cells also presented a significantly higher level of miR-4443 and miR-3620 expression than control cells.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the migration of SK-MEL-28 cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) was attenuated by adding DPG by wound-healing assay. In addition, the MMP-9 expression level was inhibited by DPG in melanoma cells stimulated by TPA and compared to only TPA-treated cells ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Anti-Migratory Effect of Dipotassium Glycyrrhizinate on Glioblastoma Cell Lines: Microarray Data for the Identification of Key MicroRNA Signatures

et al. 2022

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The nuclear factor kappa B (NF-κB) pathway has been reported to be responsible for the aggressive disease phenomenon observed in glioblastoma (GBM). Dipotassium glycyrrhizinate (DPG), a dipotassium salt of glycyrrhizic acid isolated from licorice, has recently demonstrated an anti-tumoral effect on GBM cell lines U87MG and T98G through NF-κB suppression by IRAK2- and TRAF6-mediating microRNA (miR)-16 and miR-146a, respectively. Thus, the present study aimed to evaluate the expression profiles of miRNAs related to NF-κB suppression in T98G GBM cell line after DPG exposure using miRNA microarray (Affymetrix Human miRNA 4.0A), considering only predicted miRNAs as NF-κB regulator genes. Additional assays using U251 and U138MG cells were performed to validate the array results. DPG cytotoxicity was determined by (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and cellular apoptosis was quantified by DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The anti-proliferative effect was observed by cell proliferation and wound-healing assays, and the sphere formation assay examined whether DPG reduced stem cell subpopulation formation. The most over-expressed miRNAs were miR-4443 and miR-3620. The cytotoxic effect of DPG in U251 and U138MG was observed with an IC50 of 32 and 20 mM for 48 h, respectively. The IC50 of each cell line was used in all further assays. DPG treatment-induced apoptosis is observed by DNA fragmentation and increased TUNEL-positive cells. Cell proliferation and wound-healing assays showed an anti-proliferative and anti-migratory effect by DPG on the evaluated cell lines. In addition, DPG treatment led to a 100% reduction in sphere formation. The qPCR results in U251 and U138MG cells showed that DPG increased miR-4443 (2.44 vs. 1.11, p-value = 0.11; 8.27 vs. 1.25, p-value = 0.04) and miR-3620 expression (1.66 vs. 1.00, p-value = 0.03; 8.47 vs. 1.01, p-value = 0.03) and decreased CD209 (0.44 vs. 1.10, p-value = 0.03; 0.49 vs. 1.07, p-value = 0.04) and TNC (0.20 vs. 1.03, p-value = 0.001; 0.39 vs. 1.06, p-value = 0.01) mRNA levels compared to controls. Our results suggest that DPG inhibits cell viability by activating apoptosis and inhibiting cell proliferation and stem cell subpopulation formation through miR-4443 and miR-3620 upregulation. Both miRNAs are responsible for the post-transcriptional inhibition of NF-κB by CD209 and TNC modulation.

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“…Therefore, GA can be widely used to treat many diseases, including melanoma (Su et al., 2017). There are some studies that GA can promote apoptosis, inhibit proliferation, and block migration of melanoma SK‐MEL‐28 cells (Bonafe et al., 2022; Song et al., 2013). The anticancer effect of GA is mainly achieved through inhibiting proliferation, migration, metastasis, and angiogenesis as well as inducing autophagy, apoptosis, DNA damage, and cell cycle arrest (Hussain et al., 2018; Shi et al., 2021).…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizic acid inhibits DNA damage repair and enhances cisplatin‐induced apoptosis of melanoma cells

Bian,

Niu,

et al. 2024

Chem Biol Drug Des

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This research was designed to prospect the mechanism and impact of glycyrrhizic acid (GA) on DNA damage repair and cisplatin (CP)‐induced apoptosis of melanoma cells. First, human melanoma cell SK‐MEL‐28 was stimulated using GA for 24, 48, and 72 h. Then, the optimal treatment time and dosage were selected. After that, cell counting kit‐8 (CCK‐8) was employed for testing the cell viability, flow cytometry for the apoptosis, comet assay for the DNA damage of cells, and western blot for the cleaved‐Caspase3, Caspase3, Bcl‐2, and γH2AX protein expression levels. The experimental outcomes exhibited that as the GA concentration climbed up, the SK‐MEL‐28 cell viability dropped largely, while the apoptosis level raised significantly, especially at the concentration of 100 μm. In addition, compared with GA or CPtreatment only, CP combined with GA notably suppressed the viability of melanoma cells and promoted cell apoptosis at the cytological level. At the protein level, the combined treatment notably downregulated the Bcl‐2 and Caspase3 expression levels, while significantly upregulated the cleaved‐Caspase3 and γH2AX expression levels. Besides, CP + GA treatment promoted DNA damage at the DNA molecular level. Collectively, both GA and CP can inhibit DNA damage repair and enhance the apoptosis of SK‐MEL‐28 cells, and the synergistic treatment of both exhibits better efficacy.

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Dipotassium Glycyrrhizinate on Melanoma Cell Line: Inhibition of Cerebral Metastases Formation by Targeting NF-kB Genes-Mediating MicroRNA-4443 and MicroRNA-3620—Dipotassium Glycyrrhizinate Effect on Melanoma

Cited by 6 publications

References 37 publications

Advances in the roles of glycyrrhizic acid in cancer therapy

Advances in the roles of glycyrrhizic acid in cancer therapy

Anti-Migratory Effect of Dipotassium Glycyrrhizinate on Glioblastoma Cell Lines: Microarray Data for the Identification of Key MicroRNA Signatures

Glycyrrhizic acid inhibits DNA damage repair and enhances cisplatin‐induced apoptosis of melanoma cells

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