Redox- and pH-Responsive Nanoparticles Release Piperlongumine in a Stimuli-Sensitive Manner to Inhibit Pulmonary Metastasis of Colorectal Carcinoma Cells

Lee, Hye Lim; Hwang, Sung Chul; Nah, Jae Woon; Kim, Jungsoo; Cha, Byungyoul; Kang, Dae Hwan; Jeong, Young‐Il

doi:10.1016/j.xphs.2018.06.011

Cited by 27 publications

(28 citation statements)

References 40 publications

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“…Piperlongumine (PL) exhibits significant antitumor effect in various human cancer models, including colorectal, 23 lung, 24 liver, 25 and prostate cancer. 26 Previous reports revealed that PL inhibits the activity of multiple protein kinases, attenuates angiogenesis and tumor invasion/ metastasis, 27,28 and suppresses of glycolysis. 24 Furthermore, treatment with PL induced autophagydependent cell death of human cancer cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Inhibition of ERKs/Akt-Mediated c-Fos Expression Is Required for Piperlongumine-Induced Cyclin D1 Downregulation and Tumor Suppression in Colorectal Cancer Cells</p>

Gao

Zhou

et al. 2020

OTT

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Background: Deregulation of Cyclin D1 and cell cycle progression plays a critical role in tumorigenesis. The natural compound piperlongumine (PL) exhibits potential anticancer effects in various cancer models, but the underlying mechanism needs further elucidation. Methods: The inhibitory effect of PL on colorectal cancer (CRC) cells was determined by anchorage-dependent and-independent assays. The protein level of Cyclin D1 was examined by immunoblot (IB) and immunohistochemical staining (IHC). The mRNA level was determined by qRT-PCR. Phosphorylation of histone H3 was analyzed by immunofluorescence (IF). The cell cycle was examined by flow cytometry. The in vivo antitumor effect was validated by the xenograft mouse model. Results: Cyclin D1 was overexpressed in CRC tissues and cells, and was required for maintaining cell growth, colony formation, and in vivo tumorigenesis. PL decreased the protein level of c-Fos, which eventually reduced the transcriptional activity of AP-1 and the mRNA level of Cyclin D1. Mechanism study showed that PL impaired EGF-induced activation of ERK1/2 and Akt signalings, which resulted in a reduction of c-Fos transcription. Furthermore, PL reduced the half-life of c-Fos and caused the ubiquitination-dependent degradation of c-Fos. Finally, the in vivo antitumor effect of PL on CRC cells was examined using a xenograft mouse model. Conclusion: Our data indicate that PL is a promising antitumor agent that deserves further study for CRC treatment.

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Section: Discussionmentioning

confidence: 99%

<p>Inhibition of ERKs/Akt-Mediated c-Fos Expression Is Required for Piperlongumine-Induced Cyclin D1 Downregulation and Tumor Suppression in Colorectal Cancer Cells</p>

Gao

Zhou

et al. 2020

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“…Paradoxically, an abnormal ROS level is frequently considered as a cancer-targeting strategy [ 47 ]. Even though appropriate ROS level in a tumor microenvironment is regarded as one of the major reasons for the promotion of progression and metastasis of cancer, where a higher ROS level in cancer cells than that for the survival of cancer cells induces apoptosis and/or necrosis of cancer cells [ 48 , 49 ]. For example, piperlongumine increases intracellular ROS accumulation and then depletes GSH in cancer cells [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Redox-Sensitive and Folate-Receptor-Mediated Targeting of Cervical Cancer Cells for Photodynamic Therapy Using Nanophotosensitizers Composed of Chlorin e6-Conjugated β-Cyclodextrin via Diselenide Linkage

Kim

Jeong

et al. 2021

Cells

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The aim of this study was to fabricate a reactive oxygen species (ROS)-sensitive and folate-receptor-targeted nanophotosensitizer for the efficient photodynamic therapy (PDT) of cervical carcinoma cells. Chlorin e6 (Ce6) as a model photosensitizer was conjugated with succinyl β-cyclodextrin via selenocystamine linkages. Folic acid (FA)-poly(ethylene glycol) (PEG) (FA-PEG) conjugates were attached to these conjugates and then FA-PEG-succinyl β-cyclodextrin-selenocystamine-Ce6 (FAPEGbCDseseCe6) conjugates were synthesized. Nanophotosensitizers of FaPEGbCDseseCe6 conjugates were fabricated using dialysis membrane. Nanophotosensitizers showed spherical shapes with small particle sizes. They were disintegrated in the presence of hydrogen peroxide (H2O2) and particle size distribution changed from monomodal distribution pattern to multimodal pattern. The fluorescence intensity and Ce6 release rate also increased due to the increase in H2O2 concentration, indicating that the nanophotosensitizers displayed ROS sensitivity. The Ce6 uptake ratio, ROS generation and cell cytotoxicity of the nanophotosensitizers were significantly higher than those of the Ce6 itself against HeLa cells in vitro. Furthermore, the nanophotosensitizers showed folate-receptor-specific delivery capacity and phototoxicity. The intracellular delivery of nanophotosensitizers was inhibited by folate receptor blocking, indicating that they have folate-receptor specificity in vitro and in vivo. Nanophotosensitizers showed higher efficiency in inhibition of tumor growth of HeLa cells in vivo compared to Ce6 alone. These results show that nanophotosensitizers of FaPEGbCDseseCe6 conjugates are promising candidates as PDT of cervical cancer.

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“…Induction of cell cycle arrest and apoptosis, suppression of migration and metastasis, and restriction of angiogenesis were reported to be the underlying mechanisms in PL-mediated anti-tumor activity [18,35]. PL induces G2/M phase arrest in cholangiocarcinoma and gastric carcinoma [36,37], promotes apoptosis in colon cancer in a p53dependent manner [38], inhibits the migration and metastasis in glioblastoma and other types of human cancer cells [39][40][41]. Despite the anti-tumor activity of PL being studied in the past decade, the underlying mechanism, especially the anti-tumor effect in NSCLC, remains limited.…”

Section: Discussionmentioning

confidence: 99%

Repression of Hexokinases II-Mediated Glycolysis Contributes to Piperlongumine-Induced Tumor Suppression in Non-Small Cell Lung Cancer Cells

Zhou

Yu³

et al. 2019

Int. J. Biol. Sci.

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Deregulation of glycolysis is a common phenomenon in human non-small cell lung cancer (NSCLC). In the present study, we reported the natural compound, piperlongumine, has a profound anti-tumor effect on NSCLC via regulation of glycolysis. Piperlongumine suppressed the proliferation, colony formation and HK2-mediated glycolysis in NSCLC cells. We demonstrated that exposure to piperlongumine disrupted the interaction between HK2 and VDAC1, induced the activation of the intrinsic apoptosis signaling pathway. Moreover, our results revealed that piperlongumine down-regulated the Akt signaling, exogenous overexpression of constitutively activated Akt1 in HCC827 and H1975 cells significantly rescued piperlongumine-induced glycolysis suppression and apoptosis. The xenograft mouse model data demonstrated the pivotal role of suppression of Akt activation and HK2-mediated glycolysis in mediating the in vivo antitumor effects of piperlongumine. The expression of HK2 was higher in malignant NSCLC tissues than that of the paired adjacent tissues, and was positively correlated with poor survival time. Our results suggest that HK2 could be used as a potential predictor of survival and targeting HK2 appears to be a new approach for clinical NSCLC prevention or treatment.

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Redox- and pH-Responsive Nanoparticles Release Piperlongumine in a Stimuli-Sensitive Manner to Inhibit Pulmonary Metastasis of Colorectal Carcinoma Cells

Cited by 27 publications

References 40 publications

<p>Inhibition of ERKs/Akt-Mediated c-Fos Expression Is Required for Piperlongumine-Induced Cyclin D1 Downregulation and Tumor Suppression in Colorectal Cancer Cells</p>

<p>Inhibition of ERKs/Akt-Mediated c-Fos Expression Is Required for Piperlongumine-Induced Cyclin D1 Downregulation and Tumor Suppression in Colorectal Cancer Cells</p>

Redox-Sensitive and Folate-Receptor-Mediated Targeting of Cervical Cancer Cells for Photodynamic Therapy Using Nanophotosensitizers Composed of Chlorin e6-Conjugated β-Cyclodextrin via Diselenide Linkage

Repression of Hexokinases II-Mediated Glycolysis Contributes to Piperlongumine-Induced Tumor Suppression in Non-Small Cell Lung Cancer Cells

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