Isoliquiritigenin pretreatment attenuates cisplatin induced proximal tubular cells (LLC-PK1) death and enhances the toxicity induced by this drug in bladder cancer T24 cell line

Moreno-Londoño, Ángela Patricia; Bello-Álvarez, Claudia; Pedraza‐Chaverrí, José

doi:10.1016/j.fct.2017.08.047

Cited by 25 publications

(19 citation statements)

References 63 publications

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“…ISL has been reported to enhance the toxicityinduced cell death of bladder cancer cells. Furthermore, ISL has been shown to attenuate cisplatininduced normal renal proximal tubular cell death via activation of the nuclear factor (erythroidderived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) regulatory pathway [50]. Similarly, the protective effect of ISL on the kidney and liver against cisplatin-induced colon cancer cell death has also been demonstrated [51].…”

Section: Discussionmentioning

confidence: 97%

Dietary Compound Isoliquiritigenin, an Antioxidant from Licorice, Suppresses Triple-Negative Breast Tumor Growth via Apoptotic Death Program Activation in Cell and Xenograft Animal Models

et al. 2020

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Patients with triple-negative breast cancer have few therapeutic strategy options. In this study, we investigated the effect of isoliquiritigenin (ISL) on the proliferation of triple-negative breast cancer cells. We found that treatment with ISL inhibited triple-negative breast cancer cell line (MDA-MB-231) cell growth and increased cytotoxicity. ISL reduced cell cycle progression through the reduction of cyclin D1 protein expression and increased the sub-G1 phase population. The ISL-induced apoptotic cell population was observed by flow cytometry analysis. The expression of Bcl-2 protein was reduced by ISL treatment, whereas the Bax protein level increased; subsequently, the downstream signaling molecules caspase-3 and poly ADP-ribose polymerase (PARP) were activated. Moreover, ISL reduced the expression of total and phosphorylated mammalian target of rapamycin (mTOR), ULK1, and cathepsin B, whereas the expression of autophagic-associated proteins p62, Beclin1, and LC3 was increased. The decreased cathepsin B cause the p62 accumulation to induce caspase-8 mediated apoptosis. In vivo studies further showed that preventive treatment with ISL could inhibit breast cancer growth and induce apoptotic and autophagic-mediated apoptosis cell death. Taken together, ISL exerts an effect on the inhibition of triple-negative MDA-MB-231 breast cancer cell growth through autophagy-mediated apoptosis. Therefore, future studies of ISL as a supplement or alternative therapeutic agent for clinical trials against breast cancer are warranted.

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Section: Discussionmentioning

confidence: 97%

Dietary Compound Isoliquiritigenin, an Antioxidant from Licorice, Suppresses Triple-Negative Breast Tumor Growth via Apoptotic Death Program Activation in Cell and Xenograft Animal Models

et al. 2020

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“…IsoLQ is a flavonoid with anti-inflammatory, antitumoral, and antioxidant properties [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 16 , 59 ] that exerts protective effects in liver and kidney cells [ 3 , 4 , 9 , 16 , 17 , 18 ]. In addition, it has been demonstrated that IsoLQ does not interfere with CP antineoplastic activity [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it has been described that ER stress increases the activity of antioxidant enzymes such as GR, glutathione peroxidase, and glutathione S-transferase [ 33 , 63 , 82 ]. Probably, augmented GR activity in cells pretreated with IsoLQ was due to this effect, since IsoLQ is also a bifunctional antioxidant able to induce expression of phase II detoxifying enzymes through nuclear factor erythroid 2 (Nrf2) transcriptional regulation [ 9 , 10 ]. Under ER stress, protein kinase ribonucleic acid (RNA)-activated-like ER kinase (PERK), one the of the signaling pathways of UPR, directly phosphorylates Nrf2, causing Nrf2 to dissociates from its negative regulator (Kelch-like erythroid-derived cap-n-collar homology-(ECH-)associated protein 1); after which, Nrf2 translocates to the nucleus, leading the transcription of genes that encode phase II detoxifying enzymes that maintain redox homeostasis and may contribute to cell survival [ 84 , 85 , 86 ].…”

Section: Discussionmentioning

confidence: 99%

“…LLC-PK1 cells are a proximal tubule cell line derived from porcine kidneys, widely used in experimental models [ 9 , 25 , 53 , 87 ]. LLC-PK1 cells were cultured in DMEM supplemented with 10% FBS, 0.33% NaHCO 3 , 100 U/mL penicillin, and 50 U/mL streptomycin under a humidified atmosphere of 5% CO 2 at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

“…It is used in Asia as an herbal medicine due to its anti-inflammatory, antimicrobial, antitumoral, and antioxidant properties [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Regarding its antioxidant activity, it has been reported that IsoLQ scavenges reactive oxygen species (ROS), such as the superoxide anion (O 2 ●− ), hydroxyl radical, hydrogen peroxide, and singlet oxygen [ 4 , 7 ], and induces phase II cytoprotective enzymes’ expression [ 9 , 10 ]. In addition, IsoLQ has been used as an endoplasmic reticulum (ER) stress inducer in cancer cell lines to induce apoptosis [ 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ] and also has cytoprotective effects in non-cancer cells, such as liver and kidney cells [ 1 , 4 , 9 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Isoliquiritigenin Pretreatment Induces Endoplasmic Reticulum Stress-Mediated Hormesis and Attenuates Cisplatin-Induced Oxidative Stress and Damage in LLC-PK1 Cells

et al. 2020

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Isoliquiritigenin (IsoLQ) is a flavonoid with antioxidant properties and inducer of endoplasmic reticulum (ER) stress. In vitro and in vivo studies show that ER stress-mediated hormesis is cytoprotective; therefore, natural antioxidants and ER stress inducers have been used to prevent renal injury. Oxidative stress and ER stress are some of the mechanisms of damage involved in cisplatin (CP)-induced nephrotoxicity. This study aims to explore whether IsoLQ pretreatment induces ER stress and produces hormesis to protect against CP-induced nephrotoxicity in Lilly Laboratories Cell-Porcine Kidney 1 (LLC-PK1) cells. During the first stage of this study, both IsoLQ protective concentration and pretreatment time against CP-induced toxicity were determined by cell viability. At the second stage, the effect of IsoLQ pretreatment on cell viability, ER stress, and oxidative stress were evaluated. IsoLQ pretreatment in CP-treated cells induces expression of glucose-related proteins 78 and 94 kDa (GRP78 and GRP94, respectively), attenuates CP-induced cell death, decreases reactive oxygen species (ROS) production, and prevents the decrease in glutathione/glutathione disulfide (GSH/GSSG) ratio, free thiols levels, and glutathione reductase (GR) activity. These data suggest that IsoLQ pretreatment has a moderately protective effect on CP-induced toxicity in LLC-PK1 cells, through ER stress-mediated hormesis, as well as by the antioxidant properties of IsoLQ.

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Isoliquiritigenin pretreatment regulates ER stress and attenuates cisplatin‐induced nephrotoxicity in male Wistar rats

Gómez-Sierra

Ortega-Lozano

Rojas-Morales

et al. 2023

J Biochem & Molecular Tox

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Cisplatin (CP) is a chemotherapeutic drug used to treat solid tumors. However, studies have revealed its nephrotoxic effect. Oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction are involved in CP‐induced renal damage. Thus, preconditioning (hormetic effect) of ER stress is a strategy to prevent CP‐induced renal damage. On the other hand, isoliquiritigenin (IsoLQ) is recognized as a flavonoid with antioxidant properties and an inducer of ER stress. Therefore, we evaluated the ER stress‐inducing capacity of IsoLQ and its possible protective effect against CP‐induced nephrotoxicity in adult male Wistar rats. The findings reflected that IsoLQ pretreatment might decrease renal damage by reducing plasma creatinine and blood urea nitrogen levels in animals with CP‐induced nephrotoxicity. These may be associated with IsoLQ activating ER stress and unfolded protein response (UPR). We found increased messenger RNA levels of the ER stress marker glucose‐related protein 78 kDa (GRP78). In addition, we also found that pretreatment with IsoLQ reduced the levels of CCAAT/enhancer‐binding protein‐homologous protein (CHOP) and X‐box‐binding protein 1 (XBP1) in the renal cortex, reflecting that IsoLQ can regulate the UPR and activation of the apoptotic pathway. Moreover, this preconditioning with IsoLQ of ER stress had oxidative stress‐regulatory effects, as it restored the activity of glutathione peroxidase and glutathione reductase enzymes. Finally, IsoLQ modifies the protein expression of mitofusin 2 (Mfn‐2) and voltage‐dependent anion channel (VDAC). In conclusion, these data suggest that IsoLQ pretreatment has a nephroprotective effect; it could functionally regulate the ER and mitochondria and reduce CP‐induced renal damage by attenuating hormesis‐mediated ER stress.

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Isoliquiritigenin pretreatment attenuates cisplatin induced proximal tubular cells (LLC-PK1) death and enhances the toxicity induced by this drug in bladder cancer T24 cell line

Cited by 25 publications

References 63 publications

Dietary Compound Isoliquiritigenin, an Antioxidant from Licorice, Suppresses Triple-Negative Breast Tumor Growth via Apoptotic Death Program Activation in Cell and Xenograft Animal Models

Dietary Compound Isoliquiritigenin, an Antioxidant from Licorice, Suppresses Triple-Negative Breast Tumor Growth via Apoptotic Death Program Activation in Cell and Xenograft Animal Models

Isoliquiritigenin Pretreatment Induces Endoplasmic Reticulum Stress-Mediated Hormesis and Attenuates Cisplatin-Induced Oxidative Stress and Damage in LLC-PK1 Cells

Isoliquiritigenin pretreatment regulates ER stress and attenuates cisplatin‐induced nephrotoxicity in male Wistar rats

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