Cholesterol-dependent induction of dendrite formation by ginsenoside Rh2 in cultured melanoma cells

Ota, Jun

doi:10.3892/ijmm_00000526

Cited by 4 publications

(5 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reduction of cholesterol mass or cholesterol partition coefficient causes the opposite effects in membranes (Tsamaloukas et al, 2005; Zidovetzki and Levitan, 2007). In agreement with this, we observed that induction of cholesterol depletion by membrane cholesterol extraction with Mβ CD provokes the expected reduction of fluorescence anisotropy and membrane order (Gidwani et al, 2001; Zidovetzki and Levitan, 2007; Jiang et al, 2010). Interestingly, the magnitude of the change in Δ r 38°C is considerably larger in WT animals than in APP/PS1 animals, which is consistent with the greater amount of cholesterol in lipid rafts from WT animals (Fabelo et al, 2012b).…”

Section: Discussionsupporting

confidence: 81%

Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice

Dı́az¹,

Fabelo²,

Marín³

2012

Front. Physio.

View full text Add to dashboard Cite

Alterations in the lipid composition of lipid rafts have been demonstrated both in human brain and transgenic mouse models, and it has been postulated that aberrant lipid composition in lipid rafts is partly responsible for neuronal degeneration. In order to assess the impact of lipid changes on lipid raft functional properties, we have aimed at determining relevant physicochemical modifications in lipid rafts purified from frontal cortex of wild type (WT) and APP/PS1 double transgenic mice. By means of steady-state fluorescence anisotropy analyses using two lipid soluble fluorescent probes, TMA-DPH (1-[(4-trimethyl-amino)phenyl]-6-phenyl-1,3,5-hexatriene) and DPH (1,6-diphenyl-1,3,5-hexatriene), we demonstrate that cortical lipid rafts from WT and APP/PS1 animals exhibit different biophysical behaviors, depending on genotype but also on age. Thus, aged APP/PS1 animals exhibited slightly more liquid-ordered lipid rafts than WT counterparts. Membrane microviscosity ηapp analyses demonstrate that WT lipid rafts are more fluid than APP/PS1 animals of similar age, both at the aqueous interface and hydrophobic core of the membrane. ηapp in APP/PS1 animals was higher for DPH than for TMA-DPH under similar experimental conditions, indicating that the internal core of the membrane is more viscous than the raft membrane at the aqueous interface. The most dramatic changes in biophysical properties of lipid rafts were observed when membrane cholesterol was depleted with methyl-β-cyclodextrin. Overall, our results indicate that APP/PS1 genotype strongly affects physicochemical properties of lipid raft. Such alterations appear not to be homogeneous across the raft membrane axis, but rather are more prominent at the membrane plane. These changes correlate with aberrant proportions of sphingomyelin, cholesterol, and saturated fatty acids, as well as polyunsaturated fatty acids, measured in lipid rafts from frontal cortex in this familial model of Alzheimer's Disease.

show abstract

Section: Discussionsupporting

confidence: 81%

Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice

Dı́az¹,

Fabelo²,

Marín³

2012

Front. Physio.

View full text Add to dashboard Cite

show abstract

“…As the chemical structure of Rh2 is similar to the synthetic glucocorticoid dexamethasone, it is speculated that Rh2 might bind with glucocorticoid receptor (GR) or its analogous nuclear receptor and stimulate translocation of GR [ 8 ]. Rh2 has also been shown to affect cellular functions via changing the physical properties of cholesterol-regulated membrane lipid bilayers [ 26 ] or binding the lipid portion of the cell membrane [ 27 ]. Examining whether STXBP5-AS1 is responsive to glucocorticoid would provide insight into the hormone-like regulation of STXBP5-AS1.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rh2 upregulates long noncoding RNA STXBP5-AS1 to sponge microRNA-4425 in suppressing breast cancer cell proliferation

Park

Kim

Yun

et al. 2021

Journal of Ginseng Research

View full text Add to dashboard Cite

Background Ginsenoside Rh2, a major saponin derivative in ginseng extract, is recognized for its anticancer activities. Compared to coding genes, studies on long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) that are regulated by Rh2 in cancer cells, especially on competitive endogenous RNA (ceRNA) are sparse. Methods LncRNAs whose promoter DNA methylation level was significantly altered by Rh2 were screened from methylation array data. The effect of STXBP5-AS1, miR-4425, and RNF217 on the proliferation and apoptosis of MCF-7 breast cancer cells was monitored in the presence of Rh2 after deregulating the corresponding gene. The ceRNA relationship between STXBP5-AS1 and miR-4425 was examined by measuring the luciferase activity of a recombinant luciferase/STXBP5-AS1 plasmid construct in the presence of mimic miR-4425. Results Inhibition of STXBP5-AS1 decreased apoptosis but stimulated growth of the MCF-7 cells, suggesting tumor-suppressive activity of the lncRNA. MiR-4425 was identified to have a binding site on STXBP5-AS1 and proven to be downregulated by STXBP5-AS1 as well as by Rh2. In contrast to STXBP5-AS1, miR-4425 showed pro-proliferation activity by inducing a decrease in apoptosis but increased growth of the MCF-7 cells. MiR-4425 decreased luciferase activity from the luciferase/STXBP5-AS1 construct by 26%. Screening the target genes of miR-4425 and Rh2 revealed that Rh2, STXBP5-AS1, and miR-4425 consistently regulated tumor suppressor RNF217 at both the RNA and protein level. Conclusion LncRNA STXBP5-AS1 is upregulated by Rh2 via promoter hypomethylation and acts as a ceRNA, sponging the oncogenic miR-4425. Therefore, Rh2 controls the STXBP5-AS1/miR-4425/RNF217 axis to suppress breast cancer cell growth.

show abstract

“…Fluorescence anisotropy of DPH and TMA-DPH B16 melanoma cells Induces dendrite formation in melanoma cells (Jiang et al, 2010) Increases membrane fluidity (Yi et al, 2009) Compacts the hydrophobic membrane core…”

Section: Rh2mentioning

confidence: 99%

“…Insertion into the lipid bilayer reduces the mobility of phosphatidylcholine. In melanoma cells, Rh2 decreases membrane fluidity as determined by diphenylhexatriene (DPH) fluorescence anisotropy; however, no change in fluorescence is observed with trimethylammonium diphenylhexatriene (TMA-DPH), suggesting that only the inner hydrophobic core is affected (Ota et al, 1987;Jiang et al, 2010). Ginsenoside Rg3 increases the fluorescence anisotropy of DPH and TMA-DPH in multidrug-resistant KB V20 cells but not in the parental KB cell, indicating a selective effect on cancer cell membranes (Kwon et al, 2008).…”

Section: Effect On Dynamic Membrane Propertiesmentioning

confidence: 99%

“…In addition, Rh2 has been reported to disrupt lipid rafts leading to apoptosis, either by oligomerization of the FAS death receptor in human cervical cancer HeLa cells (Yi et al, 2009) or by inactivation of the serine/threonine kinase Akt in human epidermoid carcinoma A431 and breast cancer MBA-MB-231 cells (Yi et al, 2009;Park et al, 2010). In contrast, another study showed that membrane cholesterol depletion suppresses Rh2dependent dendrite formation in melanoma cells, without affecting lipid rafts (Jiang et al, 2010). Interestingly, results suggest that ginsenoside activity is cell-type specific.…”

Section: Effect On Membrane Lateral Organizationmentioning

confidence: 99%

See 1 more Smart Citation

Lipid Membranes as Key Targets for the Pharmacological Actions of Ginsenosides

2020

View full text Add to dashboard Cite

In this review, we will focus on the activity of ginsenosides on membranes and their related effects, from physicochemical, biophysical, and pharmacological viewpoints. Ginsenosides are a class of saponins with a large structural diversity and a wide range of pharmacological effects. These effects can at least partly be related to their activity on membranes which results from their amphiphilic character. Some ginsenosides are able to interact with membrane lipids and associate into nanostructures, making them possible adjuvants for vaccines. They are able to modulate membrane biophysical properties such as membrane fluidity, permeability or the formation of lateral domains with some degree of specificity towards certain cell types such as bacteria, fungi, or cancer cells. In addition, they have shown antioxidant properties which protect membranes from lipid oxidation. They further displayed some activity on membrane proteins either through direct or indirect interaction. We investigate the structure activity relationship of ginsenosides on membranes and discuss the implications and potential use as anticancer, antibacterial, and antifungal agents.

show abstract

Cholesterol-dependent induction of dendrite formation by ginsenoside Rh2 in cultured melanoma cells

Cited by 4 publications

References 52 publications

Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice

Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice

Ginsenoside Rh2 upregulates long noncoding RNA STXBP5-AS1 to sponge microRNA-4425 in suppressing breast cancer cell proliferation

Lipid Membranes as Key Targets for the Pharmacological Actions of Ginsenosides

Contact Info

Product

Resources

About