Ailanthone increases oxidative stress in CDDP-resistant ovarian and bladder cancer cells by inhibiting of Nrf2 and YAP expression through a post-translational mechanism

Cucci, Marie Angèle; Grattarola, Margherita; Dianzani, Chiara; Damia, Giovanna; Ricci, Francesca; Roetto, Antonella; Trotta, Francesco; Barrera, Giuseppina; Pizzimenti, Stefania

doi:10.1016/j.freeradbiomed.2020.02.021

Cited by 42 publications

(33 citation statements)

References 38 publications

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“…In various types of cancers, it has been shown that the adaptive response mediated by Nrf2 contributes to the resistance towards chemotherapeutic pro-oxidant drugs, such as cisplatin (CDDP). Recently, we provided evidence on its key role in sustaining CDDP resistance in bladder cancer [ 4 , 5 , 6 ], in agreement with other reports [ 7 ]. For these reasons, Nrf2 can be a promising target to overcome chemoresistance.…”

Section: Introductionsupporting

confidence: 90%

“…Cells were incubated for 30 min with 1 µM 2′-7′-dichlorodihydrofluorescein diacetate (DCF-DA) (Invitrogen, Carlsbad, CA, USA). The amount of the fluorescent product (2,7-dichlorodihydrofluorescein, DCF) was measured using a FACScan cytometer Accuri C6 (Becton Dickinson Italia) [ 6 ].…”

Section: Methodsmentioning

confidence: 99%

“…Unfortunately, although there are several known Nrf2 pharmacological inhibitors, most of them are not very specific [ 8 , 9 ]. Besides brusatol, a plant extract able to inhibit Nrf2 expression transiently [ 10 ], we have recently demonstrated that ailanthone, a quassinoid extracted from the Ailanthus altissima plant, is a potent inhibitor of Nrf2, able to overcome the chemoresistance in bladder cancer [ 5 , 6 ]. However, both brusatol and ailanthone could produce further nonspecific responses, likely due to the off-target effects [ 6 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Besides brusatol, a plant extract able to inhibit Nrf2 expression transiently [ 10 ], we have recently demonstrated that ailanthone, a quassinoid extracted from the Ailanthus altissima plant, is a potent inhibitor of Nrf2, able to overcome the chemoresistance in bladder cancer [ 5 , 6 ]. However, both brusatol and ailanthone could produce further nonspecific responses, likely due to the off-target effects [ 6 , 11 ]. The use of a specific small interfering RNA (siRNA) targeting the Nrf2 gene is an attractive alternative, since it could entail greater specificity compared to pharmacological molecules.…”

Section: Introductionmentioning

confidence: 99%

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Carbosilane Dendrimers Loaded with siRNA Targeting Nrf2 as a Tool to Overcome Cisplatin Chemoresistance in Bladder Cancer Cells

et al. 2020

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The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as the master regulator of antioxidant and cytoprotective gene expressions. Moreover, it plays a pivotal role in cancer progression. Nrf2 mediates the adaptive response which contributes to the resistance to chemotherapeutic pro-oxidant drugs, such as cisplatin (CDDP), in various tumors, including bladder cancers. For this reason, Nrf2 could be a promising target to overcome chemoresistance. There are several known Nrf2 pharmacological inhibitors; however, most of them are not specific. The use of a specific small interfering RNA (siRNA) targeting the Nrf2 gene (siNrf2) loaded into nanovehicles is an attractive alternative, since it can increase specificity. This study aimed to evaluate the biological activity of siNrf2 loaded on guanidine-terminated carbosilane dendrimers (GCDs) in overcoming CDDP resistance in bladder cancer cells with a high level of Nrf2. Parameters such as viability, proliferation, apoptosis, migration, and oxidative stress level were taken into account. Results demonstrated that siNrf2-GCD treatment sensitized CDDP-resistant cells to CDDP treatment. Moreover, data obtained by treating the non-cancerous human kidney HK-2 cell line strongly suggest a good safety profile of the carbosilane dendrimers loaded with siNrf2. In conclusion, we suggest that siNrf2-GCD is a promising drug delivery system for gene therapy to be used in vivo; and it may represent an important tool in the therapy of CDDP-resistant cancer.

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Section: Introductionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Carbosilane Dendrimers Loaded with siRNA Targeting Nrf2 as a Tool to Overcome Cisplatin Chemoresistance in Bladder Cancer Cells

et al. 2020

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“…Recently, much attention has been directed towards the role of Nrf2 in the chemoresistance of cancer cells [ 283 ]. Nrf2 follows different routes in exerting chemoresistance, such as enhancing expression of CD99 [ 284 ], inhibiting DNA damage [ 285 ], and reducing oxidative stress-mediated damage [ 286 ]. Therefore, Nrf2 inhibition is important in reducing chemoresistance.…”

Section: Chrysin Chemotherapy and Drug Resistancementioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.

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Ailanthone suppresses cell proliferation of renal cell carcinoma partially via inhibition of EZH2

Zhu,

Dai,

Chen

et al. 2024

Discov Onc

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Ailanthone increases oxidative stress in CDDP-resistant ovarian and bladder cancer cells by inhibiting of Nrf2 and YAP expression through a post-translational mechanism

Cited by 42 publications

References 38 publications

Carbosilane Dendrimers Loaded with siRNA Targeting Nrf2 as a Tool to Overcome Cisplatin Chemoresistance in Bladder Cancer Cells

Carbosilane Dendrimers Loaded with siRNA Targeting Nrf2 as a Tool to Overcome Cisplatin Chemoresistance in Bladder Cancer Cells

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Ailanthone suppresses cell proliferation of renal cell carcinoma partially via inhibition of EZH2

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