Hyaluronated liposomes containing H2S-releasing doxorubicin are effective against P-glycoprotein-positive/doxorubicin-resistant osteosarcoma cells and xenografts

Gazzano, Elena; Buondonno, Ilaria; Marengo, Alessandro; Rolando, Barbara; Chegaev, Konstantin; Kopecka, Joanna; Saponara, Simona; Sorge, Matteo; Hattinger, Claudia Maria; Gasco, Alberto; Fruttero, Roberta; Brancaccio, Mara; Serra, Massimo; Stella, Barbara; Fattal, Elias; Berlier, Gloria; Riganti, Chiara

doi:10.1016/j.canlet.2019.04.029

Cited by 52 publications

(36 citation statements)

References 48 publications

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“…Dox, also known as adriamycin, has been considered as a first-line drug for a wide variety of cancer types, including osteosarcoma. [19][20][21][22] However, chemoresistance is a primary cause of death in patients with metastatic or recurrent osteosarcoma. 23 Thus, investigating how to decrease emergence of resistance and improve the efficacy of chemotherapeutic drugs might be important methods for treating osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

β-Elemene Enhances the Sensitivity of Osteosarcoma Cells to Doxorubicin via Downregulation of Peroxiredoxin-1

Zhang¹,

Guo²

2021

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Background Doxorubicin (Dox) resistance is a primary obstacle for the treatment of osteosarcoma. Meanwhile, β-Elemene was shown to exhibit an anti-proliferative effect on osteosarcoma cells. However, the role of a combination of Dox with β-Elemene on osteosarcoma cells remains unclear. Thus, this study aimed to investigate the role of the combination of Dox with β-Elemene on the proliferation, apoptosis and oxidative stress of Dox-resistance osteosarcoma cells. Methods CKC-8, EdU staining and flow cytometry assays were used to determine the viability, proliferation and apoptosis of Dox-resistance osteosarcoma cells, respectively. Meanwhile, the expression of antioxidant protein peroxiredoxin-1 (Prx-1) in Dox-resistance osteosarcoma cells was detected with Western blot assay. Results In this study, the inhibitory effects of Dox on the viability and proliferation of Dox-resistance osteosarcoma cells were significantly enhanced by β-Elemene. In addition, the combination of Dox and β-Elemene markedly induced the apoptosis and oxidative stress in Dox-resistance osteosarcoma cells. Moreover, combination treatment notably downregulated the expression of Prx-1 in Dox-resistance osteosarcoma cells, indicating that combination treatment inhibited the antioxidant capacity of Dox-resistance osteosarcoma cells. In vivo experiments confirmed that β-Elemene could enhance the anti-tumor effect of Dox in Saos-2/Dox xenograft model. Conclusion We found that β-Elemene could reverse Dox resistance in Dox-resistance osteosarcoma cells via inhibition of Prx-1. Therefore, combining Dox with β-Elemene might be considered as a therapeutic approach for the treatment of Dox-resistant osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

β-Elemene Enhances the Sensitivity of Osteosarcoma Cells to Doxorubicin via Downregulation of Peroxiredoxin-1

Zhang¹,

Guo²

2021

OTT

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“…Note that the reduction of the cell viability observed under light excitation (ca. 50%) is considered effective in overcoming DOX-resistance in cells expressing ABC transporters [47,48], as those used in the present work. Besides its efficacy, a plus of our approach is the absence of toxicity exerted by PS-MSNs/NOPD/DOX in the absence of irradiation.…”

Section: Discussionmentioning

confidence: 99%

“Three-Bullets” Loaded Mesoporous Silica Nanoparticles for Combined Photo/Chemotherapy

et al. 2019

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This contribution reports the design, preparation, photophysical and photochemical characterization, as well as a preliminary biological evaluation of mesoporous silica nanoparticles (MSNs) covalently integrating a nitric oxide (NO) photodonor (NOPD) and a singlet oxygen (1O2) photosensitizer (PS) and encapsulating the anticancer doxorubicin (DOX) in a noncovalent fashion. These MSNs bind the NOPD mainly in their inner part and the PS in their outer part in order to judiciously exploit the different diffusion radius of the cytotoxic NO and 1O2. Furthermore this silica nanoconstruct has been devised in such a way to permit the selective excitation of the NOPD and the PS with light sources of different energy in the visible window. We demonstrate that the individual photochemical performances of the photoactive components of the MSNs are not mutually affected, and remain unaltered even in the presence of DOX. As a result, the complete nanoconstruct is able to deliver NO and 1O2 under blue and green light, respectively, and to release DOX under physiological conditions. Preliminary biological results performed using A375 cancer cells show a good tolerability of the functionalized MSNs in the dark and a potentiated activity of DOX upon irradiation, due to the effect of the NO photoreleased.

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“…First, the accumulation of misfolded proteins induces their ubiquitination and the engulfment of proteasome/autophagosome system. Second, Pgp is folded within ER and stabilized by disulfide bonds: the interference with these processes promotes its degradation, with consequent decreased efflux of chemotherapeutic drugs and sensitization to Pgp substrates [164][165][166].…”

Section: An Altered Upr Impacts On Sensitivity To Chemotherapymentioning

confidence: 99%

Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons

Akman

Belisario

Salaroglio

et al. 2021

J Exp Clin Cancer Res

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110

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Solid tumors often grow in a micro-environment characterized by < 2% O2 tension. This condition, together with the aberrant activation of specific oncogenic patwhays, increases the amount and activity of the hypoxia-inducible factor-1α (HIF-1α), a transcription factor that controls up to 200 genes involved in neoangiogenesis, metabolic rewiring, invasion and drug resistance. Hypoxia also induces endoplasmic reticulum (ER) stress, a condition that triggers cell death, if cells are irreversibly damaged, or cell survival, if the stress is mild.Hypoxia and chronic ER stress both induce chemoresistance. In this review we discuss the multiple and interconnected circuitries that link hypoxic environment, chronic ER stress and chemoresistance. We suggest that hypoxia and ER stress train and select the cells more adapted to survive in unfavorable conditions, by activating pleiotropic mechanisms including apoptosis inhibition, metabolic rewiring, anti-oxidant defences, drugs efflux. This adaptative process unequivocally expands clones that acquire resistance to chemotherapy.We believe that pharmacological inhibitors of HIF-1α and modulators of ER stress, although characterized by low specificty and anti-cancer efficacy when used as single agents, may be repurposed as chemosensitizers against hypoxic and chemorefractory tumors in the next future.

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Hyaluronated liposomes containing H2S-releasing doxorubicin are effective against P-glycoprotein-positive/doxorubicin-resistant osteosarcoma cells and xenografts

Cited by 52 publications

References 48 publications

β-Elemene Enhances the Sensitivity of Osteosarcoma Cells to Doxorubicin via Downregulation of Peroxiredoxin-1

β-Elemene Enhances the Sensitivity of Osteosarcoma Cells to Doxorubicin via Downregulation of Peroxiredoxin-1

“Three-Bullets” Loaded Mesoporous Silica Nanoparticles for Combined Photo/Chemotherapy

Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons

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