Rosmarinic acid decreases viability, inhibits migration and modulates expression of apoptosis-related CASP8/CASP3/NLRP3 genes in human metastatic melanoma cells

Silva, Gilnei Bruno da; Mânica, Daiane; Silva, Alana Patrícia da; Marafon, Filomena; Moreno, Marcelo; Bagatini, Margarete Dulce

doi:10.1016/j.cbi.2023.110427

Cited by 15 publications

(4 citation statements)

References 47 publications

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“…In contrast to a previous report showing that RA is not toxic to PBMCs [8], our findings indicate that RA exhibits a dual effect on RBCs (Figure 1), being hemolytic at 200-800 µM and antihemolytic at 50 µM under hypotonic conditions. In addition to its oxidative potential, circulating naked Hb undergoes glomerular filtration and precipitates in kidney tubules, giving rise to renal failure [24].…”

Section: Discussioncontrasting

confidence: 99%

“…Molecules 2023, 28, 8053 2 of 17 RA exhibits anti-inflammatory, antimicrobial, anticancer, immunomodulatory, and antioxidant properties [5,6]. Importantly, RA triggers apoptosis in leukemia, breast, gastric, hepatocellular, colorectal, glioma [7], melanoma [8], prostate [9], and lung cancer cells [10][11][12]. Mechanisms involved in RA-induced apoptosis include targeting the cell cycle and DNA damage [13], histone deacetylases [9], mitochondrial Bcl-2 and Bax, caspases, PI3K/Akt/NF-κB [7], and ADAM17/EGFR/AKT/GSK3β [14].…”

Section: Introductionmentioning

confidence: 99%

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Rosmarinic Acid Elicits Calcium-Dependent and Sucrose-Sensitive Eryptosis and Hemolysis through p38 MAPK, CK1α, and PKC

Alghareeb,

Alfhili,

Alsughayyir

2023

Molecules

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Background: Rosmarinic acid (RA) possesses promising anticancer potential, but further development of chemotherapeutic agents is hindered by their toxicity to off-target tissue. In particular, chemotherapy-related anemia is a major obstacle in cancer therapy, which may be aggravated by hemolysis and eryptosis. This work presents a toxicity assessment of RA in human RBCs and explores associated molecular mechanisms. Methods: RBCs isolated from healthy donors were treated with anticancer concentrations of RA (10–800 μM) for 24 h at 37 °C, and hemolysis and related markers were photometrically measured. Flow cytometry was used to detect canonical markers of eryptosis, including phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca2+ by Fluo4/AM, cell size by FSC, and oxidative stress by H2DCFDA. Ions and pH were assessed by an ion-selective electrode, while B12 was detected by chemiluminescence. Results: RA elicited concentration-dependent hemolysis with AST and LDH release but rescued the cells from hypotonic lysis at sub-hemolytic concentrations. RA also significantly increased annexin-V-positive cells, which was ameliorated by extracellular Ca2+ removal and isosmotic sucrose. Furthermore, a significant increase in Fluo4-positive cells and B12 content and a decrease in FSC and extracellular pH with KCl efflux were noted upon RA treatment. Hemolysis was augmented by blocking KCl efflux and was blunted by ATP, SB203580, staurosporin, D4476, isosmotic urea, and PEG 8000. Conclusions: RA stimulates Ca2+-dependent and sucrose-sensitive hemolysis and eryptosis characterized by PS exposure, Ca2+ accumulation, loss of ionic regulation, and cell shrinkage. These toxic effects were mediated through energy deprivation, p38 MAPK, protein kinase C, and casein kinase 1α.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rosmarinic Acid Elicits Calcium-Dependent and Sucrose-Sensitive Eryptosis and Hemolysis through p38 MAPK, CK1α, and PKC

Alghareeb,

Alfhili,

Alsughayyir

2023

Molecules

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“…Rosmarinic acid-induced apoptosis was linked to increased caspase-8 and caspase-3 gene expression together with increased activity of caspase-3. Moreover, decreased gene expression of NLRP3 inflammasome has also been observed [240]. In another study, RA showed an inhibitory effect on melanoma cells via suppression of the ADAM17/EGFR/AKT/GSK3β axis resulting in the inhibition of melanoma cell proliferation, invasion, and migration.…”

Section: Phenolic Acidsmentioning

confidence: 87%

Spice-Derived Phenolic Compounds: Potential for Skin Cancer Prevention and Therapy

Baloghová,

Michalková,

Baranová

et al. 2023

Molecules

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Skin cancer is a condition characterized by the abnormal growth of skin cells, primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Different types of skin cancer include melanoma, basal cell carcinoma, and squamous cell carcinoma. Despite the advancements in targeted therapies, there is still a need for a safer, highly efficient approach to preventing and treating cutaneous malignancies. Spices have a rich history dating back thousands of years and are renowned for their ability to enhance the flavor, taste, and color of food. Derived from various plant parts like seeds, fruits, bark, roots, or flowers, spices are important culinary ingredients. However, their value extends beyond the culinary realm. Some spices contain bioactive compounds, including phenolic compounds, which are known for their significant biological effects. These compounds have attracted attention in scientific research due to their potential health benefits, including their possible role in disease prevention and treatment, such as cancer. This review focuses on examining the potential of spice-derived phenolic compounds as preventive or therapeutic agents for managing skin cancers. By compiling and analyzing the available knowledge, this review aims to provide insights that can guide future research in identifying new anticancer phytochemicals and uncovering additional mechanisms for combating skin cancer.

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“…It has been found that the activation of NLRP3 inflammasome is associated with human metastatic melanoma tissues [ 21 ]. It has also been found that rosmarinic acid (RA) can reduce the expression of NLRP3 inflammasome in human MM cells, suggesting that NLRP3 gene can be adopted as a target for the treatment of human MM [ 22 ]. The results suggested that the expression level of miR-22 in MCs WM239 was markedly decreased, while the expression level of NLRP3 was increased.…”

Section: Discussionmentioning

confidence: 99%

miR-22 negatively regulating NOD-like receptor protein 3 gene in the proliferation, invasion, and migration of malignant melanoma cells

Liu,

Huang,

et al. 2024

pdia

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Introduction Malignant melanoma (MM) is a highly aggressive skin tumour. Aim To investigate whether miR-22 is involved in the proliferation, invasion, and migration of melanoma cells (MCs) by negatively regulating NOD-like receptor protein 3 (NLRP3) gene. Material and methods Human MCs (WM239a) and human epidermal melanocytes (HEM) were used as study material. The expression levels of miR-22 and NLRP3 were detected by qRT-PCR. The expression of NLRP3 protein was determined by Western blot (WB) analysis. The effects of miR-22 and NLRP3 on the proliferation, invasion, and migration of MCs were evaluated by cell counting kit-8 (CCK-8), Transwell cell invasion assay, and scratch assay. Results The expression of miR-22 was clearly lower in WM239a than in HEM. Up-regulation of miR-22 expression in WM239a clearly raised the expression of miR-22, Caspase-1, and E-cadherin and the apoptotic rate of WM239a; however, the levels of interleukin-1β (IL-1β) and NLRP3, cell proliferation activity, invasion and migration ability were clearly decreased. The negative regulation of NLRP3 by miR-22 may play a major role in activities of MM. Conclusions Further studies will help to reveal the molecular details of this regulatory mechanism and provide new therapeutic strategies.

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Rosmarinic acid decreases viability, inhibits migration and modulates expression of apoptosis-related CASP8/CASP3/NLRP3 genes in human metastatic melanoma cells

Cited by 15 publications

References 47 publications

Rosmarinic Acid Elicits Calcium-Dependent and Sucrose-Sensitive Eryptosis and Hemolysis through p38 MAPK, CK1α, and PKC

Rosmarinic Acid Elicits Calcium-Dependent and Sucrose-Sensitive Eryptosis and Hemolysis through p38 MAPK, CK1α, and PKC

Spice-Derived Phenolic Compounds: Potential for Skin Cancer Prevention and Therapy

miR-22 negatively regulating NOD-like receptor protein 3 gene in the proliferation, invasion, and migration of malignant melanoma cells

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