Panaxynol, a natural Hsp90 inhibitor, effectively targets both lung cancer stem and non-stem cells

Le, Huong Thuy; Nguyen, Huy Truong; Min, Hye‐Young; Hyun, Sangwon; Kwon, Soonbum; Lee, Yeongcheol; Le, Thi Hong Van; Lee, Jeeyeon; Park, Jeong Hill; Lee, Ho-Young

doi:10.1016/j.canlet.2017.10.013

Cited by 38 publications

(33 citation statements)

References 40 publications

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“…Mechanistically, this There are opportunities to escape such a complication, as some inhibitors of HSP90 activity do not cause the HSF1 activation with subsequent expression of HSPs and MDR1. For example, KU711 [74] and panaxynol [95] were shown to inhibit HSP90 activity in CSCs without induction of HSP70 and gp170, which was correlated with better targeting of CSCs. Another relevant approach is to use HSP90 activity inhibitors in combination with other drugs, which somehow prevents the HSF1 activation/HSP induction pathway.…”

Section: Extracellular Hsp90mentioning

confidence: 95%

“…So, experimental ways to prevent or reverse EMT have been described for inhibitors of HSP90 activity, such as NVP-AUY922 [66], ganetespib [65,68], KU711, and KU757 [72]. In many research groups, the CSC-repressing and/or CSC-sensitizing effects of the inhibition of intracellular HSP90 activity were observed with geldanamycin [63,76], AR-42 (a histone deacetylase inhibitor) [87], emodin [75], 17AAG [73,74,[92][93][94], 17DMAG [79,80], NVP-AUY922 [92], WGA-TA [74], KU711 [72,74], Ku757 [72], L80 [81], and panaxynol [95]. In a system with in vitro and in vivo models, NVP-AUY922 has recently been used to inhibit the HSP90A-dependent TCL1A/Akt pathway, which confers stemness-like properties in immune-refractory tumors [27].…”

Section: Targeting Intracellular Hsp90mentioning

confidence: 99%

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Molecular Chaperones in Cancer Stem Cells: Determinants of Stemness and Potential Targets for Antitumor Therapy

Kabakov

Yakimova

Matchuk

2020

Cells

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Cancer stem cells (CSCs) are a great challenge in the fight against cancer because these self-renewing tumorigenic cell fractions are thought to be responsible for metastasis dissemination and cases of tumor recurrence. In comparison with non-stem cancer cells, CSCs are known to be more resistant to chemotherapy, radiotherapy, and immunotherapy. Elucidation of mechanisms and factors that promote the emergence and existence of CSCs and their high resistance to cytotoxic treatments would help to develop effective CSC-targeting therapeutics. The present review is dedicated to the implication of molecular chaperones (protein regulators of polypeptide chain folding) in both the formation/maintenance of the CSC phenotype and cytoprotective machinery allowing CSCs to survive after drug or radiation exposure and evade immune attack. The major cellular chaperones, namely heat shock proteins (HSP90, HSP70, HSP40, HSP27), glucose-regulated proteins (GRP94, GRP78, GRP75), tumor necrosis factor receptor-associated protein 1 (TRAP1), peptidyl-prolyl isomerases, protein disulfide isomerases, calreticulin, and also a transcription heat shock factor 1 (HSF1) initiating HSP gene expression are here considered as determinants of the cancer cell stemness and potential targets for a therapeutic attack on CSCs. Various approaches and agents are discussed that may be used for inhibiting the chaperone-dependent development/manifestations of cancer cell stemness.

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Section: Extracellular Hsp90mentioning

confidence: 95%

Section: Targeting Intracellular Hsp90mentioning

confidence: 99%

Molecular Chaperones in Cancer Stem Cells: Determinants of Stemness and Potential Targets for Antitumor Therapy

Kabakov

Yakimova

Matchuk

2020

Cells

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“…In addition, PU-H71 inhibits PI3K/mTOR pathway in Burkitt lymphoma through MYC dysregulation [198]. Panaxynol is a natural compound that elicits anti-cancer activity through inhibition of the HSP90 expression and induction of apoptosis [199]. Geldanamycin, extracted from Streptomyces hygroscopicus, elicits the anti-cancer activity through blockage of ATP-binding site of HSP90 and inhibition of its function [200].…”

Section: Colon Cancermentioning

confidence: 99%

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

Yun

Kim

Lim

et al. 2019

Cells

209

158

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Heat shock proteins (HSPs) constitute a large family of molecular chaperones classified by their molecular weights, and they include HSP27, HSP40, HSP60, HSP70, and HSP90. HSPs function in diverse physiological and protective processes to assist in maintaining cellular homeostasis. In particular, HSPs participate in protein folding and maturation processes under diverse stressors such as heat shock, hypoxia, and degradation. Notably, HSPs also play essential roles across cancers as they are implicated in a variety of cancer-related activities such as cell proliferation, metastasis, and anti-cancer drug resistance. In this review, we comprehensively discuss the functions of HSPs in association with cancer initiation, progression, and metastasis and anti-cancer therapy resistance. Moreover, the potential utilization of HSPs to enhance the effects of chemo-, radio-, and immunotherapy is explored. Taken together, HSPs have multiple clinical usages as biomarkers for cancer diagnosis and prognosis as well as the potential therapeutic targets for anti-cancer treatment.

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“…Therefore, the kidney cells treated with this polyacetylene could possibly alleviate the oxidative stress induced by cisplatin. Additionally, panaxynol previously reported a strong antiproliferative effect [19,42]. The synergetic effect of the nephroprotective and antiproliferative effect of panaxynol could be an exciting combination in cancer patients, reducing the tumor as well as protecting the kidneys from cisplatin-induced injury.…”

Section: Discussionmentioning

confidence: 99%

“…Panaxynol and panaxydol represent the two major polyacetylenes and are the major essential oil components of ginseng. Panaxynol and related polyenes have mainly demonstrated cytotoxic activity against several human tumor cell lines in vitro and in vivo [5,18,19]. Furthermore, panaxynol has exhibited anti-inflammatory and antifungal activities [20].…”

mentioning

confidence: 99%

Protective Effect of Panaxynol Isolated from Panax vietnamensis against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

Lee

Vu-Huynh

et al. 2019

Biomolecules

Self Cite

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Polyacetylenic compounds isolated from Panax species are comprised of non-polar C17 compounds, exhibiting anti-inflammatory, antitumor, and antifungal activities. Panaxynol represents the major component of the essential oils of ginseng. We investigated whether panaxynol isolated from Panax vietnamensis (Vietnamese ginseng, VG) could prevent cisplatin-induced renal damage induced in vitro and in vivo. Cisplatin-induced apoptotic cell death was observed by staining with annexin V conjugated with Alexa Fluor 488, and western blotting evaluated the molecular mechanism. Panaxynol at concentrations above 0.25 μM prevented cisplatin-induced LLC-PK1 porcine renal proximal tubular cell death. LLC-PK1 cells treated with cisplatin demonstrated an increase in apoptotic cell death, whereas pretreatment with 2 and 4 μM panaxynol decreased this effect. Cisplatin demonstrated a marked increase in the phosphorylation of c-Jun N-terminal kinase (JNK), P38, and cleaved caspase-3. However, pretreatment with 2 and 4 μM panaxynol reversed the upregulated phosphorylation of JNK, P38, and the expression of cleaved caspase-3. We confirmed that the protective effect of panaxynol isolated from P. vietnamensis in LLC-PK1 cells was at least partially mediated by reducing the cisplatin-induced apoptotic damage. In the animal study, panaxynol treatment ameliorated body weight loss and blood renal function markers and downregulated the mRNA expression of inflammatory mediators.

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Panaxynol, a natural Hsp90 inhibitor, effectively targets both lung cancer stem and non-stem cells

Cited by 38 publications

References 40 publications

Molecular Chaperones in Cancer Stem Cells: Determinants of Stemness and Potential Targets for Antitumor Therapy

Molecular Chaperones in Cancer Stem Cells: Determinants of Stemness and Potential Targets for Antitumor Therapy

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

Protective Effect of Panaxynol Isolated from Panax vietnamensis against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

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