Intracellular Ca2+ mediates lipoxygenase-induced proliferation of U-373 MG human astrocytoma cells

Kim, Jung-Ae; Chung, Young-Ja; Lee, Yong Soo

doi:10.1007/bf02976754

Cited by 12 publications

(5 citation statements)

References 34 publications

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“…In line with this, it has been reported that 5‐LOX is over‐expressed in high grade astrocytomas (Nathoo et al. 2006), and that there is a relevant role for the LOX pathway, but not for the COX pathway, in promoting cell proliferation in U‐373 MG human astrocytoma cells (Kim et al. 1998; Nathoo et al.…”

Section: Discussionmentioning

confidence: 57%

5‐Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non‐psychoactive cannabinoid

Massi

Valenti

Vaccani

et al. 2008

Journal of Neurochemistry

119

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It has been recently reported that cannabidiol (CBD), a nonpsychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation. However, the underlying biochemical mechanisms were not clarified. In the present study, we performed biochemical analysis of the effect of CBD both in vivo, by using glioma tumor tissues excised from nude mice, and in vitro, by using U87 glioma cells. In vivo exposure of tumor tissues to CBD significantly decreased the activity and content of 5-lipoxygenase (LOX, by 40%), and of its end product leukotriene B 4 ( 25%). In contrast cyclooxygenase (COX)-2 activity and content, and the amount of its end product prostaglandin E 2 , were not affected by CBD. In addition, in vivo treatment with CBD markedly stimulated ( 175%) the activity of fatty acid amide hydrolase (FAAH), the main anandamidedegrading enzyme, while decreasing anandamide content ( 30%) and binding to CB 1 cannabinoid receptors ( 25%).In vitro pre-treatment of U87 glioma cells with MK-886, a specific 5-LOX inhibitor, significantly enhanced the antimitotic effect of CBD, whereas the pre-treatment with indomethacin (pan-COX inhibitor) or celecoxib (COX-2 inhibitor), did not alter CBD effect. The study of the endocannabinoid system revealed that CBD was able to induce a concentrationdependent increase of FAAH activity in U87 cells. Moreover, a significantly reduced growth rate was observed in FAAH-overexpressing U87 cells, compared to wild-type controls. In conclusion, the present investigation indicates that CBD exerts its antitumoral effects through modulation of the LOX pathway and of the endocannabinoid system, suggesting a possible interaction of these routes in the control of tumor growth.

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Section: Discussionmentioning

confidence: 57%

5‐Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non‐psychoactive cannabinoid

Massi

Valenti

Vaccani

et al. 2008

Journal of Neurochemistry

119

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“…Ca 2+ entry through Ca 2+ channels and subsequent intracellular Ca 2+ mobilization favour tumour cell growth [105,120,121,122]. This hypothesis is in line with the fact that verapamil, a Ca 2+ channel antagonist, inhibits cell proliferation in several tumour cell lines including human smallcell carcinoma of the lung, NCI-H146 and NCI-H82 [89], H35 hepatocarcinoma cells [91] and DLD-1 carcinoma cells derived from colon cancer [92].…”

Section: Ca 2+ Entrymentioning

confidence: 86%

Roles of K + channels in regulating tumour cell proliferation and apoptosis

Wang

2004

Pfl�gers Archiv European Journal of Physiology

248

190

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K+ channels are a most diverse class of ion channels in the cytoplasmic membrane and are distributed widely in a variety of cells including cancer cells. Cell proliferation and apoptosis (programmed cell death or cell suicide) are two counterparts that share the responsibility for maintaining normal tissue homeostasis. Evidence has been accumulating from fundamental studies indicating that tumour cells possess various types of K+ channels, and that these K+ channels play important roles in regulating tumour cell proliferation and apoptosis, i.e. facilitating unlimited growth and promoting apoptotic death of tumour cells. The potential implications of K+ channels as a pharmacological target for cancer therapy and a biomarker for diagnosis of carcinogenesis are attracting increasing interest. This review aims to provide a comprehensive overview of current status of research on K+ channels/currents in tumour cells. Focus is placed on the roles of K+ channels/currents in regulating tumour cell proliferation and apoptosis. The possible mechanisms by which K+ channels affect tumour cell growth and death are discussed. Speculations are also made on the potential implications of regulation of tumour cell proliferation and apoptosis by K+ channels.

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“…In agreement with this notion, the reduction of K + efflux owing to the higher expression of tau may also attenuate apoptosis and accordingly contribute to the cell growth. Furthermore, previous finding indicated that elevated levels of intracellular Ca 2+ in response to opening of voltage-gated Ca 2+ channels (VGCC) favored tumor cell growth [ 34 , 35 , 36 ]. Thus, decreased Kv currents after tau overexpression could lead to a depolarization of membrane potential; subsequently, activation of VGCC could increase the cytoplasmic Ca 2+ levels to trigger cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Tau Downregulated the mRNA Levels of Kv Channels and Improved Proliferation in N2A Cells

et al. 2015

PLoS ONE

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Microtubule binding protein tau has a crucial function in promoting the assembly and stabilization of microtubule. Besides tuning the action potentials, voltage-gated K+ channels (Kv) are important for cell proliferation and appear to play a role in the development of cancer. However, little is known about the possible interaction of tau with Kv channels in various tissues. In the present study, tau plasmids were transiently transfected into mouse neuroblastoma N2A cells to explore the possible linkages between tau and Kv channels. This treatment led to a downregulation of mRNA levels of several Kv channels, including Kv2.1, Kv3.1, Kv4.1, Kv9.2, and KCNH4, but no significant alteration was observed for Kv5.1 and KCNQ4. Furthermore, the macroscopic currents through Kv channels were reduced by 36.5% at +60 mV in tau-tranfected N2A cells. The proliferation rates of N2A cells were also improved by the induction of tau expression and the incubation of TEA (tetraethylammonium) for 48 h by 120.9% and 149.3%, respectively. Following the cotransfection with tau in HEK293 cells, the mRNA levels and corresponding currents of Kv2.1 were significantly declined compared with single Kv2.1 transfection. Our data indicated that overexpression of tau declined the mRNA levels of Kv channels and related currents. The effects of tau overexpression on Kv channels provided an alternative explanation for low sensitivity to anti-cancer chemicals in some specific cancer tissues.

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Intracellular Ca2+ mediates lipoxygenase-induced proliferation of U-373 MG human astrocytoma cells

Cited by 12 publications

References 34 publications

5‐Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non‐psychoactive cannabinoid

5‐Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non‐psychoactive cannabinoid

Roles of K + channels in regulating tumour cell proliferation and apoptosis

Overexpression of Tau Downregulated the mRNA Levels of Kv Channels and Improved Proliferation in N2A Cells

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