Combined Antiproliferative Effects of the Aminoalkylindole WIN55,212-2 and Radiation in Breast Cancer Cells

Emery, Sean M.; Alotaibi, Moureq R.; Qing, Tao; Selley, Dana E.; Lichtman, Aron H.; Gewirtz, David A.

doi:10.1124/jpet.113.205120

Cited by 27 publications

(21 citation statements)

References 40 publications

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“…Emery et al investigated the effects of THC and CBD to modulate the growth inhibitory effects of radiation in breast cancer cell lines in culture. Both cannabinoids did not alter the anti-proliferative effects of radiation (Emery et al, 2014). However, recent studies have evaluated the efficacy of CBD, THC or combinations thereof to enhance the anti-tumor effect of radiation using an immunocompetent orthotopic murine glioma model.…”

Section: Cannabinoids In Combination With First-line Therapiesmentioning

confidence: 94%

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids

McAllister

Soroceanu

Desprez

2015

J Neuroimmune Pharmacol

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As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors. For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer. This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer stem cells. We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.

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Section: Cannabinoids In Combination With First-line Therapiesmentioning

confidence: 94%

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids

McAllister

Soroceanu

Desprez

2015

J Neuroimmune Pharmacol

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“…In ER Ϫ breast cancer cells, S1P 4 expression activated the ERK1/2 pathway and correlated with poor prognosis ( 167 ). In vitro, several breast cancer cell lines respond to S1P or S1P 1 agonist SEW2871 with increased proliferation ( 168 ).…”

Section: Nervous Systemmentioning

confidence: 99%

An update on the biology of sphingosine 1-phosphate receptors

Blaho

Hla

2014

Journal of Lipid Research

439

403

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This article is available online at http://www.jlr.org during development and ageing. S1P 1 , S1P 2 , and S1P 3 are essentially ubiquitously expressed, whereas expression of S1P 4 and S1P 5 are highly restricted to distinct cell types ( 4 ).Production of S1P can be initiated by external or internal signals, which lead to activation of the biosynthetic pathway beginning with metabolism of membrane SM to ceramide by SMases ( 5, 6 ). Ceramide, an important signaling molecule itself, can be metabolized by ceramidase to sphingosine (Sph) ( 7 ). Sph is then phosphorylated by one of two Sph kinases (Sphks), Sphk1 or Sphk2, resulting in S1P genesis ( 8-10 ) ( Fig. 1 ).Although there are proposed intracellular roles for S1P, it is often transported out of the cell where it can act in an autocrine or paracrine manner on S1PRs ( 11, 12 ). Transport out of the cell may occur via several transporters; however, the only bona fi de transporter to date is spinster 2, which is also capable of FTY720 (fi ngolimod/Gilenya; Novartis) export (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Once outside of the cell, S1P can bind to two known carriers, albumin or ApoM ( 6, 23, 24 ) ( Fig. 1 ). Approximately 35% of plasma S1P is bound to albumin and 65% to ApoM, which is found on a small percentage ( ‫ف‬ 5%) of HDL particles ( 24 ). This ApoM+HDL-bound S1P has been proposed as a primary contributor to the vasoprotective properties of HDLs ( 25-27 ). How albumin or ApoM deliver S1P to specifi c S1PRs has yet to be characterized. AGONISTS AND ANTAGONISTSThere are several well-characterized agonists and antagonists of S1PRs; however, most compounds have been diAbstract Sphingosine 1-phosphate (S1P) is a membranederived lysophospholipid that acts primarily as an extracellular signaling molecule. Signals initiated by S1P are transduced by five G protein-coupled receptors, named S1P 1-5 . Cellular and temporal expression of the S1P receptors (S1PRs) determine their specifi c roles in various organ systems, but they are particularly critical for regulation of the cardiovascular, immune, and nervous systems, with the most well-known contributions of S1PR signaling being modulation of vascular barrier function, vascular tone, and regulation of lymphocyte traffi cking. However, our knowledge of S1PR biology is rapidly increasing as they become attractive therapeutic targets in several diseases, such as chronic infl ammatory pathologies, autoimmunity, and cancer. Understanding how the S1PRs regulate interactions between biological systems will allow for greater effi cacy in this novel therapeutic strategy as well as characterization of complex physiological networks. Because of the rapidly expanding body of research, this review will focus on the most recent advances in S1PRs. Sphingosine 1-phosphate [2 S -amino-1-(dihydrogen phosphate)-4E-octadecene-1,3 R -diol] (S1P) is a simple membrane-derived lysophospholipid with regulatory roles in almost all facets of mammalian biology ( 1 ). Concentrations of S1P in blood and lymph plasmas are high, in the high...

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“…Recent studies have shown that WIN can inhibit cell proliferation in many tumour types . So we first detected the cell viability of osteosarcoma Saos‐2 cells treated by WIN.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that WIN can inhibit cell proliferation in many tumour types. 3,4 So we first detected the cell viability of osteosarcoma Saos-2 cells treated by WIN. Our result showed that the proliferation of Saos-2 cells was inhibited by WIN in a dose-dependent and time-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…WIN55,212‐2 (called WIN hereinafter), a cannabinoid receptor agonist, can significantly increase the activity of cannabinoid receptors, which are accompanied by significant anti‐tumour effects . Studies have shown that WIN can inhibit tumour cell proliferation, interfere with the normal cycle of tumour cells and induce programmed cell death. Cancers that can be inhibited by WIN include gastric cancer, lung cancer and colon cancer .…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of autophagy and enhancement of endoplasmic reticulum stress increase sensitivity of osteosarcoma Saos‐2 cells to cannabinoid receptor agonist WIN55,212‐2

Zhang

Gao

et al. 2016

Cell Biochemistry & Function

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WIN55,212-2, a cannabinoid receptor agonist, can activate cannabinoid receptors, which has proven anti-tumour effects in several tumour types. Studies showed that WIN can inhibit tumour cell proliferation and induce apoptosis in diverse cancers. However, the role and mechanism of WIN in osteosarcoma are still unclear. In this study, we examined the effect of WIN55,212-2 on osteosarcoma cell line Saos-2 in terms of cell viability and apoptosis. Meanwhile, we further explored the role of endoplasmic reticulum stress and autophagy in apoptosis induced by WIN55,212-2. Our results showed that the cell proliferation of Saos-2 was inhibited by WIN55,212-2 in a dose-dependent and time-dependent manner. WIN55,212-2-induced Saos-2 apoptosis through mitochondrial apoptosis pathway. Meanwhile, WIN55,212-2 can induce endoplasmic reticulum stress and autophagy in Saos-2 cells. Inhibition of autophagy and enhancement of endoplasmic reticulum stress increased apoptosis induced by WIN55,212-2 in Saos-2 cells. These findings indicated that WIN55,212-2 in combination with autophagic inhibitor or endoplasmic reticulum stress activator may shed new light on osteosarcoma treatment. Copyright © 2016 John Wiley & Sons, Ltd.

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Combined Antiproliferative Effects of the Aminoalkylindole WIN55,212-2 and Radiation in Breast Cancer Cells

Cited by 27 publications

References 40 publications

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids

An update on the biology of sphingosine 1-phosphate receptors

Inhibition of autophagy and enhancement of endoplasmic reticulum stress increase sensitivity of osteosarcoma Saos‐2 cells to cannabinoid receptor agonist WIN55,212‐2

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