Methyl syringate, a TRPA1 agonist represses hypoxia-induced cyclooxygenase-2 in lung cancer cells

Park, Joonwoo; Shim, Myeong Kuk; Jin, Myung; Rhyu, Mee-Ra; Lee, Young‐Joo

doi:10.1016/j.phymed.2016.01.009

Cited by 25 publications

(23 citation statements)

References 32 publications

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“…Hypoxia (HYPX) group. After keeping 24 hours in the cell same culture condition, the cells were incubated with CoCl 2 (200 μM) for 24 hours as described in previous studies 17,23,24 .…”

Section: Methodsmentioning

confidence: 99%

“…This pertains to neuronal cells, because TRP channels serve as targets for therapeutic agents that limit apoptosis 15 . Generation of hypoxia-inducible factors are high in the hypoxic conditions and they have major role in the adaptive responses to hypoxia 16 , but they are also activated by TRPA1 channel activation 16,17 . TRPM2 channel might be activated in SH-SY5Y neuronal cells by hypoxia-induced mitochondria ROS generation, although the subject still remains uninvestigated.…”

mentioning

confidence: 99%

“…Hence, we propose that modulation of TRPM2 in the RSV treatment might represent a mechanism controlling adverse neurotoxicity actions in the SH-SY5Y neuronal cells with hypoxia. One of the well-known hypoxia mimetic agents through inhibition of cellular oxygen uptake in cell line models is cobalt chloride (CoCl 2 ) 17,23,24 . It has been used in SH-SY5Y cell model for induction of hypoxia (HYPX).…”

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confidence: 99%

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Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Akyuva

Nazıroğlu

2020

Sci Rep

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Hypoxia (HYpX) induced-overload ca 2+ entry results in increase of mitochondrial oxidative stress, inflammation and apoptosis in several neurons. Ca 2+ permeable TRPM2 channel was gated by ADPribose (ADPR) and reactive oxygen species (ROS), although its activity was modulated in HYPX-exposed neurons by resveratrol (RSV). The aim of this study was to evaluate if a therapy of RSV can modulate the effect of HYPX in the TRPM2 expressing SH-SY5Y neuronal and HEK293 (no expression of TRPM2) cell lines. The SH-SY5Y and HEK293 cells were divided into four groups as control, RSV (50 μM and 24 hours), and HYPX and RSV + HYPX. For induction of HYPX in the cells, CoCl 2 (200 μM and 24 hours) incubation was used. HYPX-induced intracellular Ca 2+ responses to TRPM2 activation were increased in the SH-SY5Y cells but not in the HEK293 cells from coming H 2 o 2 and ADPR. RSV treatment improved intracellular ca 2+ responses, mitochondrial function, suppressed the generation of cytokine (IL-1β and tnf-α), cytosolic and mitochondrial ROS in the SH-SY5Y cells. Intracellular free Zn 2+ , apoptosis, cell death, PARP-1, TRPM2 expression, caspase −3 and −9 levels are increased through activating TRPM2 in the SH-SY5Y cells exposed to the HYPX. However, the values were decreased in the cells by RSV and TRPM2 blockers (ACA and 2-APB). In SH-SY5Y neuronal cells exposed to HYPX conditions, the neuroprotective effects of RSV were shown to be exerted via modulation of oxidative stress, inflammation, apoptosis and death through modulation of TRPM2 channel. RSV could be used as an effective agent in the treatment of neurodegeneration exposure to HYPX.Extensive death in neurons was induced by acute hypoxia, because disability and mortality of the neurons were increased by acute hypoxia 1 . Low blood flow to the tissue and low oxygen content of blood result in hypoxia and ischemic condition 2 . Cell survival decreased in the absence of oxygen, because ATP generation requires oxygen consumption in mitochondria 3 . Mitochondria is a main source of reactive oxygen species (ROS) generation 4 . Accumulating evidence indicates that the hypoxia and ischemic conditions result in excessive ROS generation, inflammation and apoptosis through the increase of membrane depolarization in mitochondria of neurons 5,6 . The increase of mitochondrial membrane depolarization was induced by the increase of intracellular free Ca 2+ ([Ca 2+ ] i ) concentration. Recently, hypoxia-induced mitochondria ROS generation was inhibited through modulation of voltage gated calcium channel (VGCC) in the heart cells by resveratrol (RSV) treatment 7,8 . Hence, RSV can be useful for treatment of hypoxia in neuronal cells by modulation of mitochondrial ROS generation and the subject should be clarified in the hypoxia-induced SH-SY5Y neuronal cells.Several neuronal physiological functions such as mitochondria and cell development are triggered by the changes of the [Ca 2+ ] i concentration 4 . In addition, several neurotoxicity functions such as apoptosis and inflammation in hypoxia are...

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“…Hypoxia (HYPX) group. After keeping 24 hours in the cell same culture condition, the cells were incubated with CoCl 2 (200 μM) for 24 hours as described in previous studies 17,23,24 .…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Akyuva

Nazıroğlu

2020

Sci Rep

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“…The steroidal and non-steroidal third-generation aromatase inhibitors, exemestane, letrozole and anastrozole, used in BCs, induce pain-like symptoms through TRPA1, suggesting that TRPA1 antagonists can be used for the treatment of pain associated with aromatase inhibitors [105]. Methyl syringate (100 µM), a TRPA1 agonist, has been reported to repress hypoxia-induced cyclooxygenase-2 (COX-2) in lung A549 cancer cells [106]. Methyl syringate suppresses in a TRPA1-dependent manner hypoxia-induced COX-2 and promoter activity and reduced hypoxia-induced migration and invasion and secretion of vascular endothelial growth factor.…”

Section: Trpa1 Channels In Cancer Therapymentioning

confidence: 99%

Transient Receptor Potential Cation Channels in Cancer Therapy

et al. 2019

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In mammals, the transient receptor potential (TRP) channels family consists of six different families, namely TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPA (ankyrin), that are strictly connected with cancer cell proliferation, differentiation, cell death, angiogenesis, migration, and invasion. Changes in TRP channels’ expression and function have been found to regulate cell proliferation and resistance or sensitivity of cancer cells to apoptotic-induced cell death, resulting in cancer-promoting effects or resistance to chemotherapy treatments. This review summarizes the data reported so far on the effect of targeting TRP channels in different types of cancer by using multiple TRP-specific agonists, antagonists alone, or in combination with classic chemotherapeutic agents, microRNA specifically targeting the TRP channels, and so forth, and the in vitro and in vivo feasibility evaluated in experimental models and in cancer patients. Considerable efforts have been made to fight cancer cells, and therapies targeting TRP channels seem to be the most promising strategy. However, more in-depth investigations are required to completely understand the role of TRP channels in cancer in order to design new, more specific, and valuable pharmacological tools.

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“…Of note, methyl syringate, which is suggested to be a highly specific and selective agonist of transient receptor potential ankyrin channel 1 (TRPA1) suppresses the hypoxia‐induced migration, invasion and secretion of VEGF in human lung epithelial cells (Park et al . ).…”

Section: Introductionmentioning

confidence: 97%