The oleanolic acid derivative, 3-O-succinyl-28-O-benzyl oleanolate, induces apoptosis in B16–F10 melanoma cells via the mitochondrial apoptotic pathway

Reyes‐Zurita, Fernando J.; Medina-O'Donnell, Marta; Ferrer-Martín, Rosa M.; Rufino‐Palomares, Eva E.; Martin-Fonseca, Samuel; Rivas, Francisco; Martı́nez, Antonio; Garcı́a-Granados, Andrés; Pérez‐Jiménez, Amalia; Garcı́a-Salguero, Leticia; Peragón, Juan; Mokhtari, Khalida; Medina, Pedro; Parra, Andrés; Lupiáñez, José A.

doi:10.1039/c6ra18879f

Cited by 27 publications

(24 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared with its natural precursor (OA), OADP is 718 times more effective in HepG2 cells, after 72 h of treatment [ 8 ]. Furthermore, OADP induces morphological changes that are characteristic of apoptosis [ 8 , 23 , 25 , 26 , 27 , 38 ], such as chromatin condensation and fragmentation, as evidenced by fluorescence microscopy. This effect appears to be selective for the tumor cell line, because the cytotoxicity found in the WRL68 non-tumor human embryonic liver cells was 39 times lower than in HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous studies, our groupdescribed the anticancer properties of different triterpenoids, such as maslinic acid (MA) [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ] and the OA derivative, 3- O -succinyl-28- O -benzyl oleanolate [ 27 ]. We also determined the underlying molecular mechanism associated with the anticancer effects of MA in Caco-2 and HT29 colon cancer cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Our recent studies have shown that the diamine-(PEG)ylated oleanolic acid (OADP) has strong anti-tumor effects in HCCs. In this study, we evaluated the anti-tumor mechanisms of OADP in the HepG2 HCC cell line. The cytotoxicity results showed that HepG2 cell viability was markedly reduced, with a very low 50% of cell growth inhibitory concentration (IC50, 0.14 µg/mL). We then investigated the anti-tumor mechanisms of OADP in HepG2 cells. The flow-cytometry analysis was used to evaluate cell apoptosis, indicating that 74–95% of cells were apoptotic. OADP caused cell cycle arrest in the G0/G1 phase and the loss of the mitochondrial membrane potential (MMP). Western blot analysis was performed to assess the expression levels of key proteins associated with the underlying molecular mechanism. The results showed the clear upregulation of caspase-8, caspase-9, caspase-3, Bak, p21, and p53, accompanied by the downregulation of Bcl-2. Similar results were obtained by the cotreatment with OADP and the c-Jun N-terminal kinase (JNK) inhibitor SP600125. Agents such as OADP, which are capable of activating extrinsic and intrinsic apoptotic pathways, may represent potential HCC cancer therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Traditionally, small organic molecules have been described with anti-cancer and anti-inflammatory properties useful as drugs [44,45]. Currently, has been reported that metal complexes possess remarkable advantages that render them as attractive alternatives to small organic molecules for the development of potential therapeutic agents, among others they show higher half-lives to allow their preferential tissue accumulation, due to their highest vascular permeability that permits their retention on tumor tissues [46].…”

Section: Raw 2647 Cell Viabilitymentioning

confidence: 99%

Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects

Navas

Jannus

Fernández

et al. 2020

IJMS

View full text Add to dashboard Cite

We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we determined the cytotoxicity and the anti-inflammatory potential of the cobalt compounds and ind and bum ligands in RAW 264.7 cells. Indomethacin-based metal complex was able to inhibit the NO production up to 35% in a concentration-dependent manner without showing cytotoxicity, showing around 6–37 times more effective than indomethacin. Cell cycle analysis showed that the inhibition of NO production was accompanied by a reversion of the differentiation processes in LPS-stimulated RAW 264.7 cells, due to a decreased of cell percentage in G0/G1 phase, with the corresponding increase in the number of cells in S phase. These two materials have mononuclear structures and show slow relaxation of magnetization. Moreover, both compounds show anti-diabetic activity with low in vitro cell toxicities. The formation of metal complexes with bioactive ligands is a new and promising strategy to find new compounds with high and enhanced biochemical properties and promises to be a field of great interest.

show abstract

“…MA, C 30 H 48 O 4 (2α,3β-dihydroxyolean-12-en-28-oic acid) is a natural pentacyclic triterpene, also known as crataegolic acid and derived from its structural analogue, oleanolic acid ( Figure 1 ). It is formed by 30 carbon atoms grouped into five cycles that, as substituents, have two methyl groups each on the C-4 and C-21 carbons; single methyl groups on the C-8, C-10 and C-15 carbons; two hydroxyl groups each on the C-2 and C-3 carbons; one carboxyl group on the C-28 carbon; and a double bond on the C-12 and C-13 [ 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Unveiling the Differential Antioxidant Activity of Maslinic Acid in Murine Melanoma Cells and in Rat Embryonic Healthy Cells Following Treatment with Hydrogen Peroxide

et al. 2020

Self Cite

View full text Add to dashboard Cite

Maslinic acid (MA) is a natural triterpene from Olea europaea L. with multiple biological properties. The aim of the present study was to examine MA’s effect on cell viability (by the MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key antioxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to those on healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM), whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM H2O2 was added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, which were higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in antioxidant enzyme activities depending on the cell line. In A10 cells, all the enzymes were up-regulated, but in B16F10 cells, only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to levels similar to those in the control group in both cell lines, highlighting that in A10 cells, the highest MA doses induced values lower than control. Overall, these findings demonstrate the great antioxidant capacity of MA.

show abstract

The oleanolic acid derivative, 3-O-succinyl-28-O-benzyl oleanolate, induces apoptosis in B16–F10 melanoma cells via the mitochondrial apoptotic pathway

Abstract: Antiproliferative and proapoptotic effects of 3-O-succinyl-28-O-benzyl oleanolate on B16–F10 skin-melanoma cells.

Cited by 27 publications

References 45 publications

A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells

A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells

Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects

Unveiling the Differential Antioxidant Activity of Maslinic Acid in Murine Melanoma Cells and in Rat Embryonic Healthy Cells Following Treatment with Hydrogen Peroxide

Contact Info

Product

Resources

About