Characterization of HJ-PI01 as a novel Pim-2 inhibitor that induces apoptosis and autophagic cell death in triple-negative human breast cancer

Zhao, Yuqian; Yin, Yu; Liu, Jie; Wang, Guihua; Huang, Jian; Zhu, Lingjuan; Wang, Jinhui

doi:10.1038/aps.2016.60

Cited by 14 publications

(7 citation statements)

References 38 publications

(39 reference statements)

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“…However, considering TNBCs heterogeneity, it is possible that BRCA1/2 mutations, along with AR may represent potential molecular targets in TNBCs treatment [ 75 ]. Also, Pim-2, a serin/threonine kinase strongly involved in breast cancer metastasis, may become a therapeutic target in TNBCs [ 76 ]. HJ-PI01, a Pim-2 inhibitor, seems to induce autophagic cell death and apoptosis thus decreasing malignant proliferation in TNBC cell lines [ 76 ].…”

Section: Targeted Therapy In Tnbcsmentioning

confidence: 99%

“…Also, Pim-2, a serin/threonine kinase strongly involved in breast cancer metastasis, may become a therapeutic target in TNBCs [ 76 ]. HJ-PI01, a Pim-2 inhibitor, seems to induce autophagic cell death and apoptosis thus decreasing malignant proliferation in TNBC cell lines [ 76 ]. Shindikar et al highlighted the anticancer properties of curcumin and resveratrol in TNBCs treatment, however, difficulties regarding their in vivo availability, distribution and kinetics along with a poor solubility, limits their routine use in patients [ 77 ].…”

Section: Targeted Therapy In Tnbcsmentioning

confidence: 99%

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Triple negative breast cancer: the kiss of death

et al. 2017

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One of the most controversial women malignancies, triple negative breast cancers (TNBCs) are critically overviewed here, being focused on data useful in clinical practice or to improve the therapy and patients survival. TNBCs “choose” young women and its “kiss” is, unfortunately deadly in most cases. Currently, few sparse data are available in literature concerning the origins of TNBC. Vasculogenic mimicry detected in TNBCs, seems to be determined by a population of CD133+ cells and may be stimulated by different pharmacological agents such sunitinib. Despite the fact that TNBCs do not usually metastasize through the lymphatic pathways, TNBCs may be characterized by lymphatic invasion and by an increased lymphatic microvascular density. If TNBCs treatment depends on the molecular profile of the tumor, the same statement may be postulated for TNBCs metastasis. Whether metastases have a similar phenotype as the primary tumor remains an enigma. Therefore, the question: ‘Could TNBC be subject to a standardized, unanimously accepted therapeutic strategy or is it strictly subclass-dependent?’ remains to be further investigated.

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Section: Targeted Therapy In Tnbcsmentioning

confidence: 99%

Section: Targeted Therapy In Tnbcsmentioning

confidence: 99%

Triple negative breast cancer: the kiss of death

et al. 2017

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“…Among them, we summarized 5 epidermal growth factor receptor (EGFR) inhibitors (Table ), − 4 extracellular signal regulated kinase/extracellular signal regulated kinase (MEK/ERK) inhibitors (Table ), − 4 PI3K/AKT/mTOR inhibitors (Table ), , 6 poly(ADP-ribose) polymerase (PARP) inhibitors (Table ), − 14 Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) inhibitors (Table ), ,− 3 SRC inhibitors (Table ), − 2 Unc-51-like autophagy activating kinase 1 (ULK1) inhibitors (Table ), , 5 eukaryotic elongation factor 2 kinase (eEF2K) inhibitors (Table ), − 3 bromodomain 4 (BRD4) inhibitors (Table ), − and another 40 kinase inhibitors that are currently used in clinical trials (Table ). − …”

Section: Current Status Of Candidate Small-molecule Drugs In Tnbcmentioning

confidence: 99%

Small-Molecule Drug Discovery in Triple Negative Breast Cancer: Current Situation and Future Directions

et al. 2021

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Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, but an effective targeted therapy has not been well-established so far. Considering the lack of effective targets, where do we go next in the current TNBC drug development? A promising intervention for TNBC might lie in de novo small-molecule drugs that precisely target different molecular characteristics of TNBC. However, an ideal single-target drug discovery still faces a huge challenge. Alternatively, other new emerging strategies, such as dual-target drug, drug repurposing, and combination strategies, may provide new insight into the improvement of TNBC therapeutics. In this review, we focus on summarizing the current situation of a series of candidate small-molecule drugs in TNBC therapy, including single-target drugs, dual-target drugs, as well as drug repurposing and combination strategies that will together shed new light on the future directions targeting TNBC vulnerabilities with small-molecule drugs for future therapeutic purposes.

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“…PIM2 silencing contributed to decreasing the proliferation and metastasis in non-Hodgkin lymphomas and liver cancers [10,11]. PIM inhibitors have been widely used in clinical trials for treating triple-negative human breast cancer [12] or multiple myeloma [13]. Downregulation of PIM2 lead to cell cycle arrest of lung cancer cells in G0/G1 phase [14].…”

Section: Introductionmentioning

confidence: 99%

PIM2 promotes lung adenocarcinoma cell migration by regulating XIAP/NF-κB pathway

2021

JOMH

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Background and objective: Proviral insertion site in Moloney murine leukemia virus (PIM)2 functions as a serine/threonine kinase to participate in regulating cell proliferation and cell cycle. PIM2 has been shown to be elevated in the lung cancer cell lines. This study was performed to investigate the role of PIM2 in lung adenocarcinoma cell growth. Mateial and methods: Expression level of PIM2 in lung adenocarcinoma tissues and cells was detected by qRT-PCR (quantitative Reverse Transcription PCR) and western blot. The over-expression and knockdown of PIM2 were separately established by employing pcDNA and siRNA to explore the effects on the cell viability, apoptosis, invasion and migration. The downstream pathways were evaluated by western blot assay. Results: Lung adenocarcinoma tissues and cells showed an elevation of both PIM2 mRNA and protein expression. Knocking down PIM2 decreased the cell viability and promoted the apoptosis, which can be reversed by pcDNA-mediated over-expression of PIM2. PIM2 silencing suppressed the promotional effect of over-expression of PIM2 on cell invasion and migration through increasing IκBα expression and decreasing the X-linked inhibitor of apoptosis protein (XIAP), p65 and IκBα phosphorylation. While, over-expression of PIM2 showed opposite effect on IκBα and XIAP expression or p65 and IκBα phosphorylation. Conclusion: PIM2 can not only suppress lung adenocarcinoma cell apoptosis but also promote cell migration and invasion depending on XIAP/NF-κB signaling pathway.

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Characterization of HJ-PI01 as a novel Pim-2 inhibitor that induces apoptosis and autophagic cell death in triple-negative human breast cancer

Abstract: The newly synthesized compound, HJ-PI01, can induce death receptor/mitochondrial apoptosis and autophagic cell death by targeting Pim-2 in human breast cancer cells in vitro and in vivo.

Cited by 14 publications

References 38 publications

Triple negative breast cancer: the kiss of death

Triple negative breast cancer: the kiss of death

Small-Molecule Drug Discovery in Triple Negative Breast Cancer: Current Situation and Future Directions

PIM2 promotes lung adenocarcinoma cell migration by regulating XIAP/NF-κB pathway

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