Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors

Chen, Geer; Zhu, Xiaoyu; Li, Jiaqi; Zhang, Yao; Wang, Xiaoxuan; Zhang, Ren; Qin, Xinchen; Chen, Xi; Wang, Junyi; Liao, Wei-Lin; Wu, Zongjin; Lu, Lu; Wu, Weiyu; Yu, Hongfang; Ma, Lijuan

doi:10.1016/j.phrs.2022.106487

Cited by 14 publications

(5 citation statements)

References 73 publications

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“…Histone modification refers to the post-translational modification (PTM) of amino acids in the N-terminus of histones, including histone acetylation, histone methylation, and histone ubiquitination [13]. Histone modification affects the development and prognosis of lung cancer [14], glioma [15], breast cancer [16], peripheral T-cell lymphoma [17], and rectal cancer [18]. In addition, the remodeling of damaged chromatin predicts a higher survival rate of advanced biliary tract cancer [19].…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis

Zhou,

Liu,

Wan

et al. 2024

J Hematol Oncol

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Tumor is a local tissue hyperplasia resulted from cancerous transformation of normal cells under the action of various physical, chemical and biological factors. The exploration of tumorigenesis mechanism is crucial for early prevention and treatment of tumors. Epigenetic modification is a common and important modification in cells, including DNA methylation, histone modification, non-coding RNA modification and m6A modification. The normal mode of cell death is programmed by cell death-related genes; however, recent researches have revealed some new modes of cell death, including pyroptosis, ferroptosis, cuproptosis and disulfidptosis. Epigenetic regulation of various cell deaths is mainly involved in the regulation of key cell death proteins and affects cell death by up-regulating or down-regulating the expression levels of key proteins. This study aims to investigate the mechanism of epigenetic modifications regulating pyroptosis, ferroptosis, cuproptosis and disulfidptosis of tumor cells, explore possible triggering factors in tumor development from a microscopic point of view, and provide potential targets for tumor therapy and new perspective for the development of antitumor drugs or combination therapies.

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Section: Epigenetic Modificationsmentioning

confidence: 99%

Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis

Zhou,

Liu,

Wan

et al. 2024

J Hematol Oncol

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“…These findings suggest that celastrol shows potential as a therapeutic agent for cancer treatment (Shi et al, 2020). Up to date, a large number of studies have reported that celastrol exhibits anticancer potential properties in diverse cell lines and animal models, such as in colorectal/colon cancer (Ni et al, 2019), breast cancer (Kim et al, 2011), renal cell carcinoma (Zhang et al, 2021), liver cancer (Du et al, 2020), ovarian cancer (Li et al, 2019), prostate cancer (Ji et al, 2015), lung cancer (Chen et al, 2022), and gastric cancer (Lei et al, 2022). The possible anticancer mechanisms of celastrol are the induction of cell apoptosis, cell cycle arrest, and the suppression of cell propagation (Ng et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Recent advances in drug delivery of celastrol for enhancing efficiency and reducing the toxicity

Sun,

Wang,

et al. 2024

Front. Pharmacol.

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Celastrol is a quinone methyl triterpenoid monomeric ingredient extracted from the root of Tripterygium wilfordii. Celastrol shows potential pharmacological activities in various diseases, which include inflammatory, obesity, cancer, and bacterial diseases. However, the application prospect of celastrol is largely limited by its low bioavailability, poor water solubility, and undesired off-target cytotoxicity. To address these problems, a number of drug delivery methods and technologies have been reported to enhance the efficiency and reduce the toxicity of celastrol. We classified the current drug delivery technologies into two parts. The direct chemical modification includes nucleic acid aptamer–celastrol conjugate, nucleic acid aptamer–dendrimer–celastrol conjugate, and glucolipid–celastrol conjugate. The indirect modification includes dendrimers, polymers, albumins, and vesicular carriers. The current technologies can covalently bond or encapsulate celastrol, which improves its selectivity. Here, we present a review that focalizes the recent advances of drug delivery strategies in enhancing the efficiency and reducing the toxicity of celastrol.

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“…Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb Tripterygium wilfordii [6] . The pharmacological properties of celastrol, including anti-inflammatory [7] , anti-obesity [8] , anti-depressant [9] , and anti-cancer activities [10] , have been extensively studied. Celastrol inhibits the proliferation and metastasis of various human tumor types, including gastric [11] , liver [12] , cervical [13] , and breast cancers [14] .…”

Section: Introductionmentioning

confidence: 99%

Celastrol promotes apoptosis of breast cancer MDA-MB-231 cells by targeting HSDL2

Liu,

Zhang

et al. 2024

Acupuncture and Herbal Medicine

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Objective: Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb, Tripterygium wilfordii. This study aimed to provide a scientific basis for the rational development and use of celastrol in breast cancer. Methods: A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells. Results: Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2 (HSDL2) and inhibiting its expression. Moreover, the expression of the pro-apoptotic protein, BaX, increased, the level of the anti-apoptotic protein, Bcl-2, decreased, and the rate of apoptosis increased. After the transfection of cells with si-HSDL2, the apoptosis rate was similar to that observed after the administration of celastrol. However, apoptosis was reversed by the overexpression of HSDL2. Furthermore, our MS (Mass Spectrometry) data indicated a relationship between HSDL2 and the MAPK signaling pathway. We also found that the expression of HSDL2 was directly related to the degree of ERK phosphorylation. Conclusions: Celastrol may promote apoptosis by suppressing the HSDL2/ MAPK/ERK signaling pathway.

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Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors

Cited by 14 publications

References 73 publications

Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis

Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis

Recent advances in drug delivery of celastrol for enhancing efficiency and reducing the toxicity

Celastrol promotes apoptosis of breast cancer MDA-MB-231 cells by targeting HSDL2

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