Targeting of cancer cell death mechanisms by curcumin: Implications to cancer therapy

Yu, Changqian; Yang, Bo; Najafi, Masoud

doi:10.1111/bcpt.13648

Cited by 46 publications

(20 citation statements)

References 134 publications

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“…This may be due to the concentration of cNLP used in our experiments (10 µg/mL [27 µM]). It has been previously shown that free curcumin is toxic to cancer cells ≥1 µM [ 58 ] and we have similarly demonstrated toxicity in K562 and HL-60 human leukemia cell lines treated with 15–30 µM curcumin [ 59 ]. However, since normal cells are more resistant to curcumin than cancer cells [ 47 , 48 ], presumably due to cell-cycling differences, it is therefore possible that higher curcumin concentrations (above 30 µM) may be beneficial to cell survival in quiescent cultures following IR exposures.…”

Section: Discussionsupporting

confidence: 55%

Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner

et al. 2022

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Curcumin, a natural polyphenol derived from the spice turmeric (Curcuma longa), contains antioxidant, anti-inflammatory, and anti-cancer properties. However, curcumin bioavailability is inherently low due to poor water solubility and rapid metabolism. Here, we further refined for use curcumin incorporated into “biomimetic” nanolipoprotein particles (cNLPs) consisting of a phospholipid bilayer surrounded by apolipoprotein A1 and amphipathic polymer scaffolding moieties. Our cNLP formulation improves the water solubility of curcumin over 30-fold and produces nanoparticles with ~350 µg/mL total loading capacity for downstream in vitro and in vivo applications. We found that cNLPs were well tolerated in AG05965/MRC-5 human primary lung fibroblasts compared to cultures treated with curcumin solubilized in DMSO (curDMSO). Pre-treatment with cNLPs of quiescent G0/G1-phase MRC-5 cultures improved cell survival following 137Cs gamma ray irradiations, although this finding was reversed in asynchronously cycling log-phase cell cultures. These findings may be useful for establishing cNLPs as a method to improve curcumin bioavailability for administration as a radioprotective and/or radiomitigative agent against ionizing radiation (IR) exposures in non-cycling cells or as a radiosensitizing agent for actively dividing cell populations, such as tumors.

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Section: Discussionsupporting

confidence: 55%

Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner

et al. 2022

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“…Curcumin ameliorated radiation-induced pneumonitis and pulmonary fibrosis [ 112 , 113 ] and cognitive deficits (including learning and memory defects), exerted cardioprotective, neuroprotective, hepatoprotective, and renoprotective activities [ 108 , 110 ], and decreased pain severity [ 114 ]. Additionally, curcumin has antitumor effects [ 115 ] that can synergize with radiotherapy [ 116 , 117 , 118 ]; it should thus be considered a good option to increase the efficacy of radiotherapy on cancer cells, as well as to prevent the radiotherapy-induced adverse effects in normal tissues [ 112 , 114 ]. A few human studies have confirmed its efficacy for the management of radiotherapy induced dermatitis [ 119 ] and mucositis [ 120 , 121 ].…”

Section: Medical Countermeasuresmentioning

confidence: 99%

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

et al. 2022

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Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms.

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“…Curcumin and derivatives have been proposed as potential therapeutic agents in selected cancer types such as prostate, colon, breast and thyroid cancer ( Schwertheim et al, 2017 ; Mbese et al, 2019 ) and their anticancer effects have been tested in vitro and in vivo in combination with chemotherapeutic agents and radiotherapy ( Yu et al, 2021 ). Curcumin has shown to amplify the anticancer effects of drugs (e.g., doxorubicin, cisplatin, gefitinib) and radiotherapy ( Tan and Norhaizan, 2019 ; Ashrafizadeh et al, 2020 ).…”

Section: Mechanism Of Action Of Curcumin and Related Compoundsmentioning

confidence: 99%

“…Regarding curcumin capability to activate cell death, the engagement of various pathways has been recently reported ( Yu et al, 2021 ). Besides, in the literature it is widely reported that normal cells are less sensitive to curcumin treatment than cancer cells and curcumin does not induce any apoptotic death in normal cells and tissues ( Syng-Ai et al, 2004 ).…”

Section: Mechanism Of Action Of Curcumin and Related Compoundsmentioning

confidence: 99%

Curcumin and Related Compounds in Cancer Cells: New Avenues for Old Molecules

et al. 2022

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Curcumin and related compounds are known for the large spectrum of activities. The chemical features of these compounds are important for their biological effects with a key role for the thiol-reactive α−β unsaturated carbonyl groups. Curcumin derivatives may overcome the limitation of the bioavailability of the parent compound, while maintaining the key chemical features responsible for biological activities. Curcumin and related compounds show anti-viral, anti-fungal, anti-microbial and anti-tumor activities. The therapeutic effects of curcumin, used as a supplement in cancer therapy, have been documented in various cancer types, in which inhibition of cell growth and survival pathways, induction of apoptosis and other cell death pathways have been reported. Curcumin-induced apoptosis has been linked both to the intrinsic and extrinsic apoptotic pathways. Necroptosis has also been involved in curcumin-induced toxicity. Among curcumin-induced effects, ferroptosis has also been described. The mechanism of curcumin toxicity can be triggered by reactive oxygen species-mediated endoplasmic reticulum stress. Curcumin targets have been identified in the context of the ubiquitin-proteasome system with evidence of inhibition of the proteasome proteolytic activities and cellular deubiquitinases. Curcumin has recently been shown to act on the tumor microenvironment with effects on cancer-associated fibroblasts and immune cells. The related product caffeic acid phenethyl ester has shown promising preclinical results with an effect on the inflammatory microenvironment. Here, we review the mechanisms underlying curcumin and derivatives toxicity towards cancer cells with particular emphasis on cell death pathways and the ubiquitin-proteasome system.

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Targeting of cancer cell death mechanisms by curcumin: Implications to cancer therapy

Cited by 46 publications

References 134 publications

Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner

Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

Curcumin and Related Compounds in Cancer Cells: New Avenues for Old Molecules

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