Inhibition of PIKfyve using YM201636 suppresses the growth of liver cancer via the induction of autophagy

Hou, Jiuzhou; Xi, Zhuoqing; Niu, Jie; Li, Wei; Wang, Xiao; Liang, Chao; Sun, Hua; Fang, Dong; Xie, Songqiang

doi:10.3892/or.2018.6928

Cited by 23 publications

(29 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was reported that EGF and its downstream signalling pathway MEK/ERK or PI3K/ AKT mediated the upregulation of CLDN3 expression and maintain the basic level of claudins (Zhang et al, 2017). Furthermore, YM201636-induced autophagy is dependent upon EGFR overexpression (Hou et al, 2019). Our study is consistent with previous results in terms of YM201636 induced EGFR.…”

Section: Discussionsupporting

confidence: 93%

“…Therefore, inhibition of PIKfyve was suggested as a novel target for multiple myeloma. In addition, Hou et al reported that YM201636 possess an inhibitory effect on tumour cell growth via the induction of autophagy in the hepatoma cell lines and in vivo models without any adverse effects (Hou et al, 2019). Our results showed the cytotoxic effects of YM201636 on the NSCLC cell lines and supported previous studies.…”

Section: Discussionsupporting

confidence: 91%

“…This explains the increase of claudins particularly in EGFR overactivated HCC827 cell line. Likewise, YM201636induced autophagy was associated with the presence of EGFR (Hou et al, 2019). In this case, YM201636 induced EGFR protein was in an inactive form and it was demonstrated that inactive EGFR complexes could initiate autophagy (Hou et al, 2019;Tan et al, 2015).…”

Section: Discussionmentioning

confidence: 78%

“…Hou et al demonstrated that YM201636 suppressed the growth of liver cancer cells via the induction of autophagy upon EGFR overexpression (Hou et al, 2019). Therefore, Figure 1.…”

Section: Ym201636 Induces Claudin-1 -3 And-5 Expressionsmentioning

confidence: 98%

See 3 more Smart Citations

The effects of PIKfyve inhibitor YM201636 on claudins and malignancy potential of nonsmall cell cancer cells

Dogan¹,

Düzgün²,

Yildirim³

et al. 2021

Turk J Biol

View full text Add to dashboard Cite

PIKfyve is an evolutionarily conserved lipid and protein kinase enzyme that has pleiotropic cellular functions. The aim of the present study was to investigate the effects of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) inhibitor, YM201636, on nonsmall cell lung cancer (NSCLC) cells growth, tumorigenicity, and claudin (CLDN) expressions. Three NSCLC cell lines (Calu-1, H1299 and HCC827) were used to compare the effects of YM201636. Cytotoxic effects of YM201636 were analysed using XTT assay. Malignancy potential of cells assesses with wound healing and soft agar colony-forming assays. mRNA and protein expressions of claudins were analysed by qRT-PCR and immunofluorescence staining. Our results revealed that YM201636 inhibited the proliferation and malignancy potential of Calu-1, H1299, and HCC827 cells in a dose-dependent manner. After YM201636 treatment CLDN1, -3 and -5 expressions increased significantly in HCC827 cells. CLDN3 and -5 expressions also significantly increased in Calu1 cell line. YM201636 treatment significantly reduced the CLDN1 and increased the CLDN5 expression in H1299 cells. Immunofluorescence staining of CLDN1, -3 and -5 proteins showed a significant increase after YM201636 treatment. Besides, YM201636 induced EGFR mRNA expression in all NSCLC cell lines. Our results have shown that YM201636 inhibits tumorigenicity of NSCLC cells. Furthermore, estimated glomerular filtration rate (EGFR) pathway is important signalling involved in the regulation of claudins. Understanding the mechanisms of PIKfyve inhibitors may improve cancer treatment particularly for EGFR overactivated NSCLC.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 78%

“…Hou et al demonstrated that YM201636 suppressed the growth of liver cancer cells via the induction of autophagy upon EGFR overexpression (Hou et al, 2019). Therefore, Figure 1.…”

Section: Ym201636 Induces Claudin-1 -3 And-5 Expressionsmentioning

confidence: 98%

See 2 more Smart Citations

The effects of PIKfyve inhibitor YM201636 on claudins and malignancy potential of nonsmall cell cancer cells

Dogan¹,

Düzgün²,

Yildirim³

et al. 2021

Turk J Biol

View full text Add to dashboard Cite

show abstract

“…Apilimod, a potent inhibitor of PIKfyve35, can significantly reduce the entry of SARS-CoV S pseudovirus into 293/hACE2 cells via early endosomes in a dose-dependent manner [49]. Treating 293/ hACE2 cells with another PIKfyve inhibitor, YM201636 [72], also had a similar effect. Moreover, a major downstream effector of PI (3,5)P2, two-pore channel subtype 2 (TPC2) [73], is important for SARS-CoV-2 entry, and tetrandrine (an inhibitor of TPC2) inhibits the activity of SARS-CoV-2 S pseudovirus.…”

Section: Fusion Inhibitorsmentioning

confidence: 94%

Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19

et al. 2020

View full text Add to dashboard Cite

Coronavirus disease 2019 is a newly emerging infectious disease currently spreading across the world. It is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2, while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain. In this review, we highlight recent research advance in the structure, function and development of antivirus drugs targeting the S protein.

show abstract

PIKFYVE inhibitors trigger interleukin‐24‐dependent cell death of autophagy‐dependent melanoma

Roy,

Chakraborty,

DePamphilis

2024

Molecular Oncology

View full text Add to dashboard Cite

Inhibitors specifically targeting the 1‐phosphatidylinositol 3‐phosphate 5‐kinase (PIKFYVE) disrupt lysosome homeostasis, thereby selectively terminating autophagy‐dependent human cancer cells in vivo as well as in vitro without harming the viability of nonmalignant cells. To elucidate the mechanism by which PIKFYVE inhibition induces cell death, autophagy‐dependent melanoma cells were compared with normal foreskin fibroblasts. RNA sequence profiling suggested that PIKFYVE inhibitors upregulated an endoplasmic reticulum (ER) stress response involving interleukin‐24 (IL24; also known as MDA7) selectively in melanoma cells. Subsequent biochemical and genetic analyses confirmed these results and extended them to tumor xenografts in which tumor formation and expansion were inhibited. IL24 expression was upregulated by the DDIT3/CHOP/CEBPz transcription factor, a component of the PERK‐dependent ER‐stress response. Ectopic expression of IL24‐induced cell death in melanoma cells, but not in foreskin fibroblasts, whereas ablation of the IL24 gene in melanoma cells prevented death. IL24 upregulation was triggered specifically by PIKFYVE inhibition. Thus, unlike thapsigargin and tunicamycin, which induce ER‐stress indiscriminately, PIKFYVE inhibitors selectively terminated PIKFYVE‐sensitive melanoma by inducing IL24‐dependent ER‐stress. Moreover, induction of cell death by a PIKFYVE inhibitor together with ectopic expression of IL24 protein was cumulative, thereby confirming the therapeutic potential of PIKFYVE inhibitors in the treatment of melanoma.

show abstract

Inhibition of PIKfyve using YM201636 suppresses the growth of liver cancer via the induction of autophagy

Cited by 23 publications

References 33 publications

The effects of PIKfyve inhibitor YM201636 on claudins and malignancy potential of nonsmall cell cancer cells

The effects of PIKfyve inhibitor YM201636 on claudins and malignancy potential of nonsmall cell cancer cells

Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19

PIKFYVE inhibitors trigger interleukin‐24‐dependent cell death of autophagy‐dependent melanoma

Contact Info

Product

Resources

About