Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application

Shi, Jinfeng; Li, Jiaxin; Xu, Ziyi; Chen, Liang; Luo, Rui; Zhang, Chen; Gao, Fei; Zhang, Jinming; Fu, Chaomei

doi:10.3389/fphar.2020.558741

Cited by 110 publications

(80 citation statements)

References 181 publications

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“…Due to deleterious side-effects of chemically synthesized therapeutics, especially anticancer; natural products are plausible alternatives and it is urgently needed to find safer natural remedies. 35 , 47–49 Celastrol is a natural product obtained from Tripterygium wilfordii Hook F and was stated for its anticancer activities. Significantly, celastrol showed anticancer activity against various tumors as breast, prostate, and liver cancers, multiple myeloma, and glioma.…”

Section: Discussionmentioning

confidence: 99%

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation

Youns¹,

Askoura²,

Abbas³

et al. 2021

OTT

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Background Pancreatic cancer is one of the most serious and lethal human cancers with a snowballing incidence around the world. The natural product celastrol has also been widely documented as a potent anti-inflammatory, anti-angiogenic, and anti-oxidant. Purpose To elucidate the antitumor effect of celastrol on pancreatic cancer cells and its modulatory role on whole genome expression. Methods The antitumor activity of celastrol on a panel of pancreatic cancer cells has been evaluated by Sulforhodamine B assay. Caspase 3/7 and histone-associated DNA fragments assays were done for apoptosis measurement. Additionally, prostaglandin (PGE2) inhibition was evaluated. Moreover, a microarray gene expression profiling was carried out to detect possible key players that modulate the antitumor effects of celastrol on cells of pancreatic cancer. Results Our findings indicated that celastrol suppresses the cellular growth of pancreatic cancer cells, induces apoptosis, and inhibits PGE2 production. Celastrol modulated many signaling genes and its cytotoxic effect was mainly mediated via over-expression of ATF3 and DDIT3 , and down-expression of RRM2 and MCM4 . Conclusion The current study aims to be a starting point to generate a hypothesis on the most significant regulatory genes and for a full dissection of the celastrol possible effects on each single gene to prevent the pancreatic cancer growth.

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Section: Discussionmentioning

confidence: 99%

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation

Youns¹,

Askoura²,

Abbas³

et al. 2021

OTT

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“…It has gained importance over the past two decades due to its potent anti-inflammatory (Pinna et al, 2004;Shaker et al, 2014;Ma et al, 2015), anti-cancer [gastric and ovarian cancers (Xu et al, 2019;, cervical cancer (Zhou et al, 2017), and hepatocellular carcinoma Du et al, 2020)], neuroprotective (Paris et al, 2010;Jiang et al, 2018), and anti-oxidant (Cleren et al, 2005) activities. However, albeit potent, its clinical translation is impeded due to two main disadvantages that are poor water solubility of 0.044 mg/ml at 25°C (BCS class IV drug) (Yang et al, 2019), which limits its bioavailability, and high systemic toxicity resulting from its narrow therapeutic index (Zhang et al, 2014;Shi et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications

et al. 2021

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Celastrol (also called tripterine) is a quinone methide triterpene isolated from the root extract of Tripterygium wilfordii (thunder god vine in traditional Chinese medicine). Over the past two decades, celastrol has gained wide attention as a potent anti-inflammatory, anti-autoimmune, anti-cancer, anti-oxidant, and neuroprotective agent. However, its clinical translation is very challenging due to its lower aqueous solubility, poor oral bioavailability, and high organ toxicity. To deal with these issues, various formulation strategies have been investigated to augment the overall celastrol efficacy in vivo by attempting to increase the bioavailability and/or reduce the toxicity. Among these, nanotechnology-based celastrol formulations are most widely explored by pharmaceutical scientists worldwide. Based on the survey of literature over the past 15 years, this mini-review is aimed at summarizing a multitude of celastrol nanoformulations that have been developed and tested for various therapeutic applications. In addition, the review highlights the unmet need in the clinical translation of celastrol nanoformulations and the path forward.

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“…The two natural pentacyclic triterpenoids celastrol and pristimerin are commonly found in the roots and bark of Celastraceae species. Both compounds show a wide range of pharmacological activities, including anti-cancer, anti-inflammatory, antioxidant, hepatoprotective, or immunomodulatory, among others [ 4 , 5 , 6 , 7 , 8 ]. The anti-cancer properties of celastrol, one of the most studied methylene quinones, have been attributed to apoptosis and autophagy induction, cell cycle arrest, and anti-metastatic and anti-angiogenic action [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Activity and Mode of Action of Celastrol, a Nortriterpen Quinone Isolated from Natural Sources

Padilla-Montaño

Guerra

Moujir

2021

Foods

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Species of the Celastraceae family are traditionally consumed in different world regions for their stimulating properties. Celastrol, a triterpene methylene quinone isolated from plants of celastraceas, specifically activates satiety centers in the brain that play an important role in controlling body weight. In this work, the antimicrobial activity and mechanism of action of celastrol and a natural derivative, pristimerin, were investigated in Bacillus subtilis. Celastrol showed a higher antimicrobial activity compared with pristimerin, being active against Gram-positive bacteria with minimum inhibitory concentrations (MICs) that ranged between 0.16 and 2.5 µg/mL. Killing curves displayed a bactericidal effect that was dependent on the inoculum size. Monitoring of macromolecular synthesis in bacterial populations treated with these compounds revealed inhibition in the incorporation of all radiolabeled precursors, but not simultaneously. Celastrol at 3 µg/mL and pristimerin at 10 µg/mL affected DNA and RNA synthesis first, followed by protein synthesis, although the inhibitory action on the uptake of radiolabeled precursors was more dramatic with celastrol. This compound also caused cytoplasmic membrane disruption observed by potassium leakage and formation of mesosome-like structures. The inhibition of oxygen consumption of whole and disrupted cells after treatments with both quinones indicates damage in the cellular structure, suggesting the cytoplasmic membrane as a potential target. These findings indicate that celastrol could be considered as an interesting alternative to control outbreaks caused by spore-forming bacteria.

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Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application

Cited by 110 publications

References 181 publications

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation

Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications

Antimicrobial Activity and Mode of Action of Celastrol, a Nortriterpen Quinone Isolated from Natural Sources

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