Bortezomib induces apoptosis and autophagy in osteosarcoma cells through mitogen-activated protein kinase pathway <i>in vitro</i>

Lou, Zhidong; Ren, Tingting; Peng, Xiaojin; Sun, Yifeng; Jiao, Guangjun; Lu, Qiong; Zhang, Shuai; Lu, Xin; Guo, Wei

doi:10.1177/0300060513490618

Cited by 33 publications

(36 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4A) reduced the level of soluble PARK2. It has been recently shown that bortezomib treatment leads to activation of autophagy (32,33); hence, we conclude from these data that mutant PARK2 C289G may be primarily degraded through autophagy under such conditions. However, bortezomib treatment significantly (albeit not completely) reduced the protective effects of HSPB1 and HSPB4 on PARK2 C289G aggregation, while having only a modest effect on HSPB7-mediated protection and no effect on HSPB2-mediated protection (Fig.…”

Section: Hspb1supporting

confidence: 53%

HSPA1A-Independent Suppression of PARK2 C289G Protein Aggregation by Human Small Heat Shock Proteins

Minoia

Grit

Kampinga

2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

The C289G mutation of the parkin E3-ubiquitin protein ligase (PARK2) is associated with autosomal recessive juvenile onset Parkinson's disease and was found to be associated with protein aggregation. Members of the human small heat shock proteins (HSPBs) have been implicated in protein degradation and prevention of protein aggregation. In this study, we show that of the 10 HSPB members, individual overexpression of HSPB1, HSPB2, HSPB4, and HSPB7 suppresses PARK2 C289G-associated protein aggregation. Intriguingly, the protective actions of these HSPBs are not impaired upon inactivation of the ATP-dependent HSP70 chaperone machines. Depending on the HSPB member the protective actions involve either autophagic or proteasomal degradation pathways.

show abstract

Section: Hspb1supporting

confidence: 53%

HSPA1A-Independent Suppression of PARK2 C289G Protein Aggregation by Human Small Heat Shock Proteins

Minoia

Grit

Kampinga

2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Recent experimental and clinical data have shown that proteasome inhibitors serve as a new and promising class of anticancer agents [21,24,77,79,84,87,144]. However, the data presented in this review proved beyond doubt that proteasome inhibition induces www.fhc.viamedica.pl autophagy in the majority of cells.…”

Section: Final Remarksmentioning

confidence: 76%

“…According to Ding et al [75], JNK but not XBP-1 seems to be involved in the induction of autophagy after treatment with proteasome inhibitors. In a subsequent study these authors observed that increased autophagy in HOS cells in response to bortezomib corresponded with altered levels of intracellular mitogen-activated protein kinase (MAPK) signalling molecules such as decreased levels of phosphorylated MAPK kinase (MEK1/2) and extracellular signal-regulated kinase (ERK1/2), and simultaneous increase of phosphorylated JNK and p38 MAPK [77]. Also, after exposure of melanoma cells to bortezomib, no changes were observed in the total expression levels of IRE1, ASK1, JNK and p38, however, this proteasome inhibitor triggered the phosphorylation of these proteins [24].…”

Section: Unfolded Protein Responsementioning

confidence: 96%

“…Increased cellular levels of LC3-II and Beclin-1 proteins were found after bortezomib treatment of human glioblastoma U251 and U87 cells [74], melanoma cells [24], several cell lines of head and neck squamous cell carcinoma [76] and human osteosarcoma (HOS) cells [77]. In human colon cancer HCT116 cells and murine embryonic fibroblasts (MEFs) bortezomib increased www.fhc.viamedica.pl expression of LC3-II but did not lead to significant changes in Beclin-1 levels [75].…”

Section: Effects Of Different Classes Of Proteasome Inhibitors On Autmentioning

confidence: 99%

“…During proteasomal inhibition ELAVL1/HuR was up-regulated at both mRNA and protein levels, and was shown to bind with and post-transcriptionally regulate p62/SQSTM1 mRNA [132]. On the other hand, substantial decreases in p62/SQSTM1 levels after proteasomal inhibition in human osteosarcoma (HOS) cells have been reported [77]. Also, after treatment of human dopaminergic neuroblastoma SH-SY5Y cells with the proteasome inhibitor lactacystin, and in dopaminergic neurons obtained from a UPS-impaired mouse model of Parkinson's disease, significantly reduced levels of p62/ /SQSTM1 were found [85].…”

Section: Formation Of Aggresomesmentioning

confidence: 99%

See 2 more Smart Citations

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

Wójcik

2014

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Abstract:The Ubiquitin-Proteasomes System (UPS) and autophagy, two main intracellular protein degradation pathways within the eukaryotic cells which were originally regarded as rather independent, seem to be very closely related. Proteasome inhibitors, including the multipathway inhibitor bortezomib, are drawing increased attention for their therapeutic potential in the treatment of chronic inflammation and cancer, especially tumours with a high degree of malignancy. The over-activation of autophagy induces cell death and may act as a powerful tumour-suppressing mechanism. However, autophagy, serving as an important mechanism to generate nutrients in time of cellular stresses, may directly contribute to the survival of cells treated with proteasome inhibitors, and in consequence, may decrease the effectiveness of therapy. Results of studies performed on several cancer cell lines demonstrated synergy between proteasome inhibitors and autophagy inhibitors. Those results became the base for ongoing clinical trials investigating autophagy inhibition in combination with anti-cancer therapies, including bortezomib. This review provides summary of the latest data on the functioning of the UPS and the mechanisms of autophagy. The new insights describing the main pathways of autophagy activation in response to UPS inhibition related to: (i) Unfolded Protein Response, (ii) PI3K/Akt/mTOR pathway, and (iii) formation of aggresomes, are discussed. It is concluded that concomitant inhibition of the two main cellular protein degradation systems may provide new therapeutic modalities for cancer treatment.

show abstract

Downregulation of microRNA‐143‐5p is required for the promotion of odontoblasts differentiation of human dental pulp stem cells through the activation of the mitogen‐activated protein kinases 14‐dependent p38 mitogen‐activated protein kinases signaling pathway

Wang

Nan

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

MicroRNAs (miRNAs) play critical roles in various biological processes including cell differentiation. Some researchers suggested that the p38 mitogen-activated protein kinases (MAPK) signaling pathway had an effect on regulating the odontoblastic differentiation of human dental pulp stem cells (hDPSCs). This study focuses on the effects of miR-143-5p on hDPSCs by regulating the p38 MAPK signaling pathway. The targeting relationship of MAPK14 and miR-143-5p targets were verified by TargetScan and dual-luciferase reporter gene assay. Through overexpression of miR-143-5p or silencing of miR-143-5p, expressions of miR-143-5p, MAPK14, Ras, MAPK kinase (MKK) 3/6, dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), and osteocalcin (OCN) were detected by reverse transcription quantitative polymerase chain reaction. Protein expressions of MAPK14, Ras, and MKK3/6 were determined by western blot analysis. ALP and alizarin red S staining were used to detect mineralization. Initially, MAPK14 was found to be negatively regulated by miR-143-5p. Meanwhile, the upregulated miR-143-5p decreased the p38 MAPK signaling pathway related genes (MAPK14, Ras, and MKK3/6) and odontoblastic differentiation markers (ALP, DSPP, and OCN) expression. On the contrary, the downregulated miR-143-5p increased the p38 MAPK signaling pathway related genes (MAPK14, Ras, and MKK3/6) and odontoblastic differentiation markers (ALP, DSPP, and OCN) expression. Furthermore, ALP activity and mineralized nodules increased after downregulation of miR-143-5p, and after its upregulation, ALP activity and mineralized nodules decreased. Our data suggest that poor expression of miR-143-5p promotes hDPSCs odontoblastic differentiation through the activation of the p38 MAPK signaling pathway by upregulating MAPK14. K E Y W O R D S human dental pulp stem cells (hDPSCs), mitogen-activated protein kinases (MAPK) 14, microRNA-143-5p (miR-143-5p), odontoblastic differentiation, p38 MAPK signaling pathway J Cell Physiol. 2019;234:4840-4850. wileyonlinelibrary.com/journal/jcp 4840 |

show abstract

Bortezomib induces apoptosis and autophagy in osteosarcoma cells through mitogen-activated protein kinase pathway in vitro

Abstract: This study provided new insights into the mechanisms underlying bortezomib-induced apoptosis in human osteosarcoma HOS cells, and suggests that bortezomib could be a potent chemotherapeutic agent in the treatment of osteosarcoma.

Cited by 33 publications

References 30 publications

HSPA1A-Independent Suppression of PARK2 C289G Protein Aggregation by Human Small Heat Shock Proteins

HSPA1A-Independent Suppression of PARK2 C289G Protein Aggregation by Human Small Heat Shock Proteins

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

Downregulation of microRNA‐143‐5p is required for the promotion of odontoblasts differentiation of human dental pulp stem cells through the activation of the mitogen‐activated protein kinases 14‐dependent p38 mitogen‐activated protein kinases signaling pathway

Contact Info

Product

Resources

About