Synthesis of a Resveratrol Analogue with High Ceramide-Mediated Proapoptotic Activity on Human Breast Cancer Cells

Minutolo, Filippo; Sala, G; Bagnacani, A.; Bertini, Simone; Carboni, I; Placanica, Giorgio; Prota, Giovanni; Rapposelli, Simona; Sacchi, Nicoletta; Macchia, Marco; Ghidoni, Riccardo

doi:10.1021/jm050528k

Cited by 69 publications

(42 citation statements)

References 21 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results were in agreement with the literature since it was clearly shown that both caspases and mitochondrial membrane potential are wellknown downstream targets of ceramides (12). By our group and some other groups it was reported that resveratrol application results in increases in endogenous ceramide concentrations in prostate, breast (27), and colorectal carcinoma (2) and acute promyelocytic leukemia cells (28). Increases in intracellular concentrations of ceramides were shown by expression levels of the LASS gene family, GCS and SK-1 genes, and direct detection of ceramides by LC-MS.…”

Section: Discussionsupporting

confidence: 93%

Resveratrol Triggers Apoptosis Through Regulating Ceramide Metabolizing Genes in Human K562 Chronic Myeloid Leukemia Cells

Kartal

Saydam

Şahin

et al. 2011

Nutrition and Cancer

View full text Add to dashboard Cite

Resveratrol, an important phytoalexin in many plants, has been reported to have cytotoxic effects on various types of cancer. Ceramide is a bioactive sphingolipid that regulates many signaling pathways, including cell growth and proliferation, senescence and quiescence, apoptosis, and cell cycle. Ceramides are generated by longevity assurance genes (LASS). Glucosylceramide synthase (GCS) and sphingosine kinase-1 (SK-1) enzymes can convert ceramides to antiapoptotic molecules, glucosylceramide, and sphingosine-1-phosphate, respectively. C8:ceramide, an important cell-permeable analogue of natural ceramides, increases intracellular ceramide levels significantly, while 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and SK-1 inhibitor increase accumulation of ceramides by inhibiting GCS and SK-1, respectively. Chronic myelogenous leukemia (CML) is a hematological disorder resulting from generation of BCR/ABL oncogene. In this study, we examined the roles of ceramide metabolizing genes in resveratrolinduced apoptosis in K562 CML cells. There were synergistic cytotoxic and apoptotic effects of resveratrol with coadministration of C8:ceramide, PDMP, and SK-1 inhibitor. Interestingly, there were also significant increases in expression levels of LASS genes and decreases in expression levels of GCS and SK-1 in K562 cells in response to resveratrol. Our data, in total, showed for the first time that resveratrol might kill CML cells through increasing intracellular generation and accumulation of apoptotic ceramides.

show abstract

Section: Discussionsupporting

confidence: 93%

Resveratrol Triggers Apoptosis Through Regulating Ceramide Metabolizing Genes in Human K562 Chronic Myeloid Leukemia Cells

Kartal

Saydam

Şahin

et al. 2011

Nutrition and Cancer

View full text Add to dashboard Cite

show abstract

“…Firstly, resveratrol increases ceramide to induce apoptosis in colon, breast and prostate cancer cells. Similarly, synthetic resveratrol analogues with minor sidechain modifications induce ceramide-dependent apoptosis (Minutolo et al 2005). The effect of resveratrol is through increased de novo ceramide biosynthesis and is reversed by SPT inhibitors (Dolfini et al 2007;Sala et al 2003;Scarlatti et al 2003Scarlatti et al , 2007Ulrich et al 2007).…”

Section: Cancer and Inflammationmentioning

confidence: 99%

Resveratrol and its oligomers: modulation of sphingolipid metabolism and signaling in disease

et al. 2014

View full text Add to dashboard Cite

Resveratrol, a natural compound endowed with multiple health-promoting effects, has received much attention given its potential for the treatment of cardiovascular, inflammatory, neurodegenerative, metabolic and age-related diseases. However, the translational potential of resveratrol has been limited by its specificity, poor bioavailability and uncertain toxicity. In recent years, there has been an accumulation of evidence demonstrating that resveratrol modulates sphingolipid metabolism. Moreover, resveratrol forms higher order oligomers that exhibit better selectivity and potency in modulating sphingolipid metabolism. This review evaluates the evidence supporting the modulation of sphingolipid metabolism and signaling as a mechanism of action underlying the therapeutic efficacy of resveratrol and oligomers in diseases, such as cancer.

show abstract

“…Minutolo et al [28] compared the biological effects of seven naphthalene-based and/or methoxylated resveratrol analogues with resveratrol. They found that compound 3 (Scheme 1) exerts an antiproliferative effect via a ceramide-mediated proapoptotic mechanism, with an increase of endogenous ceramide coupled to cleavage of PARP (poly-(ADP-ribose)-polymerase).…”

Section: Synthesis Of Resveratrol Derivatives With Anticancer Activitymentioning

confidence: 99%

Synthetic Resveratrol Derivatives and Their Biological Activities: A Review

Liu¹,

Liu²,

Chen³

et al. 2015

OJMC

View full text Add to dashboard Cite

Resveratrol, a naturally derived stilbene that exists in various foods and beverages, has attracted extensive exploration due to its multiple biological activities, such as anticancer, antioxidant, cardiovascular protection, anti-inflammatory, antiviral, chemopreventive effect, neuroprotective effect, immunomodulation and so on. However, owing to its poor oral bioavailability, the application of resveratrol is greatly restricted. Because of that, a large amount of efforts had been made by researchers on designing its derivatives to obtain compounds with improved efficiency and low toxicity for developing more active drugs for clinical application. In this report, we review the current development of studying on resveratrol derivatives including their properties and activities. Additionally, this article also presents the synthetic routes of correlative resveratrol derivatives.

show abstract

Synthesis of a Resveratrol Analogue with High Ceramide-Mediated Proapoptotic Activity on Human Breast Cancer Cells

Cited by 69 publications

References 21 publications

Resveratrol Triggers Apoptosis Through Regulating Ceramide Metabolizing Genes in Human K562 Chronic Myeloid Leukemia Cells

Resveratrol Triggers Apoptosis Through Regulating Ceramide Metabolizing Genes in Human K562 Chronic Myeloid Leukemia Cells

Resveratrol and its oligomers: modulation of sphingolipid metabolism and signaling in disease

Synthetic Resveratrol Derivatives and Their Biological Activities: A Review

Contact Info

Product

Resources

About