Resveratrol activates autophagic cell death in prostate cancer cells via downregulation of STIM1 and the mTOR pathway

Selvaraj, Senthil; Sun, Yuyang; Sukumaran, Pramod; Singh, Brij B.

doi:10.1002/mc.22324

Cited by 147 publications

(112 citation statements)

References 69 publications

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“…It is also noteworthy that the mode of sustained Ca 2+ cyt rise in CUR+CA-treated AML cells is distinct from those proposed for polyphenols. Specifically, elevation of Ca 2+ cyt did not involve the previously reported modulation of store-operated [45] or voltage-dependent [46] Ca 2+ entry because the removal of extracellular Ca 2+ did not affect the extent of CUR+CA-induced apoptosis (Figure 3A). Likewise, accumulation of Ca 2+ cyt did not result solely from massive Ca 2+ ER release despite the fact that CUR is a known inhibitor of SERCA [43].…”

Section: Discussionmentioning

confidence: 62%

Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid

et al. 2016

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Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by extremely heterogeneous molecular and biologic abnormalities that hamper the development of effective targeted treatment modalities. While AML cells are highly sensitive to cytotoxic Ca2+ overload, the feasibility of Ca2+- targeted therapy of this disease remains unclear. Here, we show that apoptotic response of AML cells to the synergistically acting polyphenols curcumin (CUR) and carnosic acid (CA), combined at low, non-cytotoxic doses of each compound was mediated solely by disruption of cellular Ca2+ homeostasis. Specifically, activation of caspase cascade in CUR+CA-treated AML cells resulted from sustained elevation of cytosolic Ca2+ (Ca2+cyt) and was not preceded by endoplasmic reticulum stress or mitochondrial damage. The CUR+CA-induced Ca2+cyt rise did not involve excessive influx of extracellular Ca2+ but, rather, occurred due to massive Ca2+ release from intracellular stores concomitant with inhibition of Ca2+cyt extrusion through the plasma membrane. Notably, the CUR+CA combination did not alter Ca2+ homeostasis and viability in non-neoplastic hematopoietic cells, suggesting its cancer-selective action. Most importantly, co-administration of CUR and CA to AML-bearing mice markedly attenuated disease progression in two animal models. Collectively, our results provide the mechanistic and translational basis for further characterization of this combination as a prototype of novel Ca2+-targeted pharmacological tools for the treatment of AML.

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Section: Discussionmentioning

confidence: 62%

Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid

et al. 2016

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“…Resveratrol has been shown to be capable of reducing cancer growth in previous studies [38–41]. However, these studies use very high doses of the compound, for example Dann et al [38] used 100 μM and Ji et al [39] used up to 200 μM.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol and acetyl-resveratrol modulate activity of VEGF and IL-8 in ovarian cancer cell aggregates via attenuation of the NF-κB protein

et al. 2016

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BackgroundKey features of advanced ovarian cancer include metastasis via cell clusters in the abdominal cavity and increased chemoresistance. Resveratrol and derivatives of resveratrol have been shown to have antitumour properties. The purpose of this study was to investigate the effect of resveratrol and acetyl-resveratrol on 3D cell aggregates of ovarian cancer, and establish if NF-κB signalling may be a potential target.MethodsPoly-HEMA coated wells were used to produce 3D aggregates of two ovarian cancer cell lines, SKOV-3 and OVCAR-5. The aggregates were exposed to 10, 20 or 30 μM resveratrol or acetyl-resveratrol for 2, 4 or 6 days. Cell growth and metabolism were measured then ELISA, western blot and immunofluorescence were utilised to evaluate VEGF, IL-8 and NF-κB levels.ResultsResveratrol and acetyl-resveratrol reduced cell growth and metabolism of SKOV-3 aggregates in a dose- and time-dependent manner. After 6 days all three doses of both compounds inhibited cell growth. This growth inhibition correlated with the attenuated secretion of VEGF and a decrease of NF-κB protein levels. Conversely, the secretion of IL-8 increased with treatment. The effects of the compounds were limited in OVCAR-5 cell clusters.ConclusionsThe results suggest that resveratrol and its derivative acetyl-resveratrol may inhibit in vitro 3D cell growth of certain subtypes of ovarian cancer, and growth restriction may be associated with the secretion of VEGF under the control of the NF-κB protein.

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“…[19] It has been reported to modulate several signaling pathways to control the growth of cancer cells. [20] In addition, resveratrol has shown to attenuate several voltage gated ion channels in several cell lines. Mainly resveratrol inhibited voltage gated sodium current in rat prostate cancer cell line (MAT-LyLu) [11] and Kv1.3 in human lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

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Malathi

2017

AJP

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Background: Phenolic compounds are ubiquitous in dietary fruits and vegetables and have been proposed to have antioxidant, antibacterial, anti-inflammatory, and anticancer effects. Voltage gated K + channels (I K ) contribute to various cellular mechanisms involved in the tumor cell progression. Therefore, the modulation of I K current may be a potential target for cancer therapy. In this study, we electrophysiologically characterized four phenolic compounds for their modulatory activities on I K currents. Materials and Methods: The whole cell configuration of the patch clamp recording technique was used to record the I K currents from human prostate cancer line (LNCaP). In addition, 200 µM of phenolic compounds (curcumin, resveratrol, rutin, and troxerutin) were externally perfused to the cells. Results: Obtained results provide evidence that resveratrol at 200 µM inhibited more than half of the I K current amplitude. On the other hand, curcumin, rutin, and troxerutin did not show any modulatory effect on I K current in LNCaP cells. Conclusion: This study demonstrates that not all the anticancer compounds are effective inhibitors of I K current, but only few of them. The I K current inhibitors might exhibit effective antimetastatic properties.

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Resveratrol activates autophagic cell death in prostate cancer cells via downregulation of STIM1 and the mTOR pathway

Cited by 147 publications

References 69 publications

Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid

Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid

Resveratrol and acetyl-resveratrol modulate activity of VEGF and IL-8 in ovarian cancer cell aggregates via attenuation of the NF-κB protein

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