Indispensable Role of Protein Turnover in Autophagy, Apoptosis and Ubiquitination Pathways

Abosheasha, Mohammed A.; Khalik, Eman A. M. Abd El; El‐Gowily, Afnan H.

doi:10.1007/7515_2020_31

Cited by 1 publication

(3 citation statements)

References 61 publications

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“…Each immunosuppressed mouse was injected with (2 × 10 6 tumor cells/0.2 mL) orthotopic intradermally [14,84] into the 4th mammary fat pad. When the tumor size grew up to approx.~150-250 mm 3 , the mice were randomly divided into different groups (according to experimental design). DOX and CQ were dissolved in sterile PBS to prepare an appropriate experimental dose, while 1mg of TIC was dissolved in 0.1% dimethyl sulfoxide DMSO as stock solutions and then diluted to the appropriate doses in sterile PBS before the experiment.…”

Section: In Vivo Cytotoxic Activity In Xenografting Mice Model Inducementioning

confidence: 99%

“…After injecting mice with cells, during the experiment tumor sizes were measured using a digital caliper with a vernier to reach a tumor size of 150-250 mm 3 ; the mice were randomly divided into eight groups (15 mice per group) divided as follows: GPI: Naïve (Control healthy mice injected with 0.2 mL of saline), GPII: MCF-7 group; (injected with 2 × 10 6 MCF-7 cells. ), GPIII: DOX group (MCF-7 cells and DOX (2 mg/Kg; i.p.)…”

Section: Experimental Design Of Mcf-7 Tumor Development In Vivo Modelmentioning

confidence: 99%

“…Apoptosis is regulated by intracellular and/or extracellular signals; hence, the caspase’s activation is considered a potential therapeutic target against human cancer diseases [ 3 ]. Autophagy is a major pathway in all eukaryotic cells and is considered as a multistep process in which cytoplasm, intracellular organelles, and proteins are sequestered through the fusion of autophagosomes with lysosomes forming autolysosomes, with ultimate degradation by lysosomal hydrolases, while autophagy has a crucial role as an emerging cell survival process [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

et al. 2021

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Cancer is a complex devastating disease with enormous treatment challenges, including chemo- and radiotherapeutic resistance. Combination therapy demonstrated a promising strategy to target hard-to-treat cancers and sensitize cancer cells to conventional anti-cancer drugs such as doxorubicin. This study aimed to establish molecular profiling and therapeutic efficacy assessment of chloroquine and/or tioconazole (TIC) combination with doxorubicin (DOX) as anew combination model in MCF-7 breast cancer. The drugs are tested against apoptotic/autophagic pathways and related redox status. Molecular docking revealed that chloroquine (CQ) and TIC could be potential PI3K and ATG4B pathway inhibitors. Combination therapy significantly inhibited cancer cell viability, PI3K/AkT/mTOR pathway, and tumor-supporting autophagic flux, however, induced apoptotic pathways and altered nuclear genotoxic feature. Our data revealed that the combination cocktail therapy markedly inhibited tumor proliferation marker (KI-67) and cell growth, along with the accumulation of autophagosomes and elevation of LC3-II and p62 levels indicated autophagic flux blockage and increased apoptosis. Additionally, CQ and/or TIC combination therapy with DOX exerts its activity on the redox balance of cancer cells mediated ROS-dependent apoptosis induction achieved by GPX3 suppression. Besides, Autophagy inhibition causes moderately upregulation in ATGs 5,7 redundant proteins strengthened combinations induced apoptosis, whereas inhibition of PI3K/AKT/mTOR pathway with Beclin-1 upregulation leading to cytodestructive autophagy with overcome drug resistance effectively in curing cancer. Notably, the tumor growth inhibition and various antioxidant effects were observed in vivo. These results suggest CQ and/or TIC combination with DOX could act as effective cocktail therapy targeting autophagy and PI3K/AKT/mTOR pathways in MCF-7 breast cancer cells and hence, sensitizes cancer cells to doxorubicin treatment and combat its toxicity.

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Section: In Vivo Cytotoxic Activity In Xenografting Mice Model Inducementioning

confidence: 99%

Section: Experimental Design Of Mcf-7 Tumor Development In Vivo Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

Indispensable Role of Protein Turnover in Autophagy, Apoptosis and Ubiquitination Pathways

Cited by 1 publication

References 61 publications

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

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