Involvement of endoplasmic reticulum in paclitaxel‐induced apoptosis

Liao, Pei‐Chun; Tan, Sai-Koong; Lieu, Chien-Hui; Jung, Hsuan‐Kuang

doi:10.1002/jcb.21730

Cited by 77 publications

(76 citation statements)

References 36 publications

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“…Adaptation to ER stress conditions represents a mechanism of resistance to taxanes [8][9][10]; interestingly, our data show that paclitaxel induces apoptotic cell death and caspase 12 activation in MCF7 BC cells and enhances BiP/Grp78 and Grp94 expression [7]. Also in this context, a role of TRAP1 has been demonstrated by our groups: in fact, paclitaxel induces TRAP1 protein levels in MCF7 and MDA-MB231 BC cells, without affecting its mRNA expression.…”

supporting

confidence: 72%

ER stress protection in cancer cells: the multifaceted role of the heat shock protein TRAP1

Matassa

Arzeni

Landriscina

et al. 2014

Endoplasmic Reticulum Stress in Diseases

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Abbreviations TRAPis involved in ER stress protection of cancer cellsTRAP1 (Tumour Necrosis Factor Receptor-Associated Protein 1) is a molecular chaperone, member of the HSP90 family, that contributes to the overall survival of cancer cells and is up-regulated in most tumour types (reviewed in 1). A large body of literature demonstrates that TRAP1 is part of a pro-survival signalling pathway aimed at evading the toxic effects of oxidants and anticancer drugs and plays a role in protecting mitochondria against apoptotic stimuli (reviewed in 2). However, whether its roles are uniformly oncogenic or not is now a matter of intense debate. Interestingly, Yoshida and colleagues [3] propose a more subtle reading of TRAP1 roles in the regulation of cellular metabolism and its impact on tumorigenesis. In fact, an inverse correlation between TRAP1 expression and tumor stage in cervical, bladder, and clear cell renal cell carcinoma was demonstrated. These conflicting observations on TRAP1 "behaviour" in different biological contexts is strictly related to a specific molecular complex/integrated network in which TRAP1 represents one of the focal nodes.Abstract: TRAP1 is an HSP90 chaperone, upregulated in human cancers and involved in organelles' homeostasis and tumor cell metabolism. Indeed, TRAP1 is a key regulator of adaptive responses used by highly proliferative tumors to face the metabolic stress induced by increased demand of protein synthesis and hostile environments. Besides well-characterized roles in prevention of mitochondrial permeability transition pore opening and in regulating mitochondrial respiration, TRAP1 is involved in novel regulatory mechanisms: i) the attenuation of global protein synthesis, ii) the co-translational regulation of protein synthesis and ubiquitination of specific client proteins, and iii) the protection from Endoplasmic Reticulum stress. This provides a crucial role to TRAP1 in maintaining cellular homeostasis through protein quality control, by avoiding the accumulation of damaged or misfolded proteins and, likely, facilitating the synthesis of selective cancer-related proteins. Herein, we summarize how these regulatory mechanisms are part of an integrated network, which enables cancer cells to modulate their metabolism and to face, at the same time, oxidative and metabolic stress, oxygen and nutrient deprivation, increased demand of energy production and macromolecule biosynthesis. The possibility to undertake a new strategy to disrupt such networks of integrated control in cancer cells holds great promise for treatment of human malignancies.

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confidence: 72%

ER stress protection in cancer cells: the multifaceted role of the heat shock protein TRAP1

Matassa

Arzeni

Landriscina

et al. 2014

Endoplasmic Reticulum Stress in Diseases

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“…16,17) In the present study, paclitaxel induced the expression of CHOP, an ER stress marker, 19) in the sciatic nerves of the mice and in the LY-PPB6 cells; however, this effect was inhibited by aucubin. The comparison of the inhibitory action of aucubin in in vivo and in vitro studies is difficult.…”

Section: )contrasting

confidence: 48%

“…16,17) Therefore, the aim of this study was to investigate whether aucubin alleviates paclitaxel-induced nerve activity and ER stress in mice.…”

Section: Abstract Paclitaxel; Mechanical Allodynia; Aucubin; Firing;mentioning

confidence: 99%

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Prophylactic Administration of Aucubin Inhibits Paclitaxel-Induced Mechanical Allodynia <i>via</i> the Inhibition of Endoplasmic Reticulum Stress in Peripheral Schwann Cells

Andoh

Uta

Kato

et al. 2017

Biological & Pharmaceutical Bulletin

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Paclitaxel is a chemotherapeutic agent that causes peripheral neuropathy as its major dose-limiting side effect. However, the peripheral neuropathy is difficult to manage. A study we recently conducted showed that repetitive administration of aucubin as a prophylactic inhibits paclitaxel-induced mechanical allodynia. However, the mechanisms underlying the anti-allodynic activity of aucubin, which is a major component of Plantaginis Semen, was unclear. In addition to mechanical allodynia, aucubin inhibited spontaneous and mechanical stimuli-induced firing in spinal dorsal horn neurons; however, catalpol, a metabolite of aucubin, did not show these effects. Furthermore, paclitaxel induced the expression of CCAAT/enhancer-binding protein homologous protein, a marker of endoplasmic reticulum (ER) stress, in the sciatic nerve and a Schwann cell line (LY-PPB6 cells); however, this effect was inhibited by aucubin. These results suggest that aucubin inhibits paclitaxel-induced mechanical allodynia through the inhibition of ER stress in peripheral Schwann cells. Key words paclitaxel; mechanical allodynia; aucubin; firing; Schwann cell; stressPaclitaxel is an anti-microtubule agent originally isolated from the bark of the Pacific yew tree (Taxus brevifolia) and is wildly used to treat solid neoplasms such as breast, ovarian, and lung cancers.1,2) However, in spite of its useful anticancer effect, paclitaxel causes peripheral neuropathy, which is characterized by mechanical allodynia, spontaneous pain, shooting and burning pain, tingling, and numbness, with a stocking-and-glove distribution.3) The peripheral neuropathy is a major dose-limiting side effect, which disturbs cancer treatment with paclitaxel. Therefore, relief of the neuropathy is very important for improving both the QOL and cancer treatment with paclitaxel. Several drugs, including gabapentin and amifostine, have failed to relieve paclitaxel-induced peripheral neuropathy [4][5][6] ; therefore, alternative therapeutic agents are need.Goshajinkigan is a traditional herbal formulation that consists of 10 herbal medicines (Rehmanniae Radix, Achyranthis Radix, Corni Fructus, Dioscoreae Rhizoma, Plantaginis Semen, Alismatis Rhizoma, Poria, Moutan Cortex, Cinnamoni Cortex, and Processi Aconiti Radix). It has been shown to attenuate the progression of peripheral neuropathy induced by docetaxel and paclitaxel/carboplatin treatments in cancer patients.7,8) Our previous study has been shown that repetitive administration of goshajinkigan extract as a prophylactic inhibits the exacerbation of paclitaxel-induced mechanical allodynia in mice.9) We also showed that aucubin, which is an iridoid glycoside and the main component of Plantaginis Semen, plays an important role in the anti-allodynic action of goshajinkigan.10) However, the mechanisms underlying the anti-allodynic activity of aucubin are not understood completely. It was reported in a previous study that paclitaxel decreased peripheral blood flow and induced mechanical allodynia in mice.11) The study also demonstra...

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“…Analogous to mitochondrial release of cytochrome c, BH3-only proteins can induce ER Ca 2 þ release, dependent on BAX/BAK, and associated with their activation/oligomerization Nieto-Miguel et al, 2007;Liao et al, 2008). This process can be inhibited by the overexpression of BCL-2/BCLxL at the ER, likely due to sequestration of either BH3-only proteins or BAX/BAK .…”

Section: Discussionmentioning

confidence: 99%

The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family

2008

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Involvement of endoplasmic reticulum in paclitaxel‐induced apoptosis

Cited by 77 publications

References 36 publications

ER stress protection in cancer cells: the multifaceted role of the heat shock protein TRAP1

ER stress protection in cancer cells: the multifaceted role of the heat shock protein TRAP1

Prophylactic Administration of Aucubin Inhibits Paclitaxel-Induced Mechanical Allodynia <i>via</i> the Inhibition of Endoplasmic Reticulum Stress in Peripheral Schwann Cells

The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family

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