Effects of rapamycin and AZD3463 combination on apoptosis, autophagy, and cell cycle for resistance control in breast cancer

Özateş, Neslihan Pınar; Söğütlü, Fatma; Lerminoglu, Ferzan; Demir, Busra; Gündüz, Cumhur; Shademan, Behrouz; Avcı, Çığır Biray

doi:10.1016/j.lfs.2020.118643

Cited by 19 publications

(15 citation statements)

References 30 publications

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“…In cancer, FOXO1 was activated by ROS to regulate autophagy and mitochondrial oxidative metabolism [ 121 , 122 ]. In breast cancer, the level of FOXO3 can be induced by rapamycin, AZD3463, and AZD-RAPA, accompanied by autophagy formation [ 123 ]. Hopkins’ group reported that FOXO3 could be regulated by peroxidase peroxiredoxin 1 to control Let-7b and Let-7c , affecting cell migration ability.…”

Section: Possible Connections Between Let-7 -Mediated Glycolysis and Autophagy In Cancer Progressionmentioning

confidence: 99%

The Metabolism Reprogramming of microRNA Let-7-Mediated Glycolysis Contributes to Autophagy and Tumor Progression

Liao

2021

IJMS

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Cancer is usually a result of abnormal glucose uptake and imbalanced nutrient metabolization. The dysregulation of glucose metabolism, which controls the processes of glycolysis, gives rise to various physiological defects. Autophagy is one of the metabolic-related cellular functions and involves not only energy regeneration but also tumorigenesis. The dysregulation of autophagy impacts on the imbalance of metabolic homeostasis and leads to a variety of disorders. In particular, the microRNA (miRNA) Let-7 has been identified as related to glycolysis procedures such as tissue repair, stem cell-derived cardiomyocytes, and tumoral metastasis. In many cancers, the expression of glycolysis-related enzymes is correlated with Let-7, in which multiple enzymes are related to the regulation of the autophagy process. However, much recent research has not comprehensively investigated how Let-7 participates in glycolytic reprogramming or its links to autophagic regulations, mainly in tumor progression. Through an integrated literature review and omics-related profiling correlation, this review provides the possible linkage of the Let-7 network between glycolysis and autophagy, and its role in tumor progression.

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Section: Possible Connections Between Let-7 -Mediated Glycolysis and Autophagy In Cancer Progressionmentioning

confidence: 99%

The Metabolism Reprogramming of microRNA Let-7-Mediated Glycolysis Contributes to Autophagy and Tumor Progression

Liao

2021

IJMS

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“…AZD3463 exhibits an anticancer effect as a potential ALK/IGF1R inhibitor and induces apoptosis and autophagy by regulating the PI3K/AKT/mTOR pathway. The co-treatment of AZD3463 and rapamycin increases the efficacy of anticancer therapy via the induction of apoptosis autophagy and reduction of cell proliferation in breast cancer cells [184]. Isoliquiritigenin (ISL) is derived from a flavonoid from Glycyrrhiza glabra and shows anticancer effects both in vivo and in vitro.…”

Section: The Effect Of Autophagy Inducers In Anticancer Therapymentioning

confidence: 99%

The Dual Role of Autophagy in Cancer Development and a Therapeutic Strategy for Cancer by Targeting Autophagy

Yun¹,

Jeon²,

et al. 2020

IJMS

101

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Autophagy is a delicate intracellular degradation process that occurs due to diverse stressful conditions, including the accumulation of damaged proteins and organelles as well as nutrient deprivation. The mechanism of autophagy is initiated by the creation of autophagosomes, which capture and encapsulate abnormal components. Afterward, autophagosomes assemble with lysosomes to recycle or remove degradative cargo. The regulation of autophagy has bipolar roles in cancer suppression and promotion in diverse cancers. Furthermore, autophagy modulates the features of tumorigenesis, cancer metastasis, cancer stem cells, and drug resistance against anticancer agents. Some autophagy regulators are used to modulate autophagy for anticancer therapy but the dual roles of autophagy limit their application in anticancer therapy, and present as the main reason for therapy failure. In this review, we summarize the mechanisms of autophagy, tumorigenesis, metastasis, cancer stem cells, and resistance against anticancer agents. Finally, we discuss whether targeting autophagy is a promising and effective therapeutic strategy in anticancer therapy.

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“…Thus, although DZNep can suppress breast cancer, it simultaneously increases osteolysis. To prevent osteoclastic resorption, we introduced another anti-cancer agent, AZD3463, that promisingly induced apoptosis by inhibiting the PI3K-Akt pathway in breast cancer (Hu et al, 2020;Ozates et al, 2021), neuroblastoma (Wang et al, 2016), glioblastoma (Asik et al, 2020;Goker Bagca et al, 2020), acute myeloid leukemia (Moharram et al, 2019), and Ewing sarcoma (Sampson et al, 2015). Akt activation is associated with worse outcomes in endocrine-related breast cancer (Pérez-Tenorio et al, 2002), so targeting this signaling pathway is a classic research focus (Guerrero-Zotano et al, 2016;Costa et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Combination of AZD3463 and DZNep Prevents Bone Metastasis of Breast Cancer by Suppressing Akt Signaling

Cao

Rong

et al. 2021

Front. Pharmacol.

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Osteolysis resulting from osteoclast overactivation is one of the severe complications of breast cancer metastasis to the bone. Previous studies reported that the anti-cancer agent DZNep induces cancer cell apoptosis by activating Akt signaling. However, the effect of DZNep on breast cancer bone metastasis is unknown. We previously found that DZNep enhances osteoclast differentiation by activating Akt. Therefore, we explored the use of the anti-cancer agent AZD3463 (an Akt inhibitor) along with DZNep, as AZD3463 can act as an anti-cancer agent and can also potentially ameliorate bone erosion. We evaluated osteoclast and breast cancer cell phenotypes and Akt signaling in vitro by treating cells with DZNep and AZD3463. Furthermore, we developed a breast cancer bone metastasis animal model in mouse tibiae to further determine their combined effects in vivo. Treatment of osteoclast precursor cells with DZNep alone increased osteoclast differentiation, bone resorption, and expression of osteoclast-specific genes. These effects were ameliorated by AZD3463. The combination of DZNep and AZD3463 inhibited breast cancer cell proliferation, colony formation, migration, and invasion. Finally, intraperitoneal injection of DZNep and AZD3463 ameliorated tumor progression and protected against bone loss. In summary, DZNep combined with AZD3463 prevented skeletal complications and inhibited breast cancer progression by suppressing Akt signaling.

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Effects of rapamycin and AZD3463 combination on apoptosis, autophagy, and cell cycle for resistance control in breast cancer

Cited by 19 publications

References 30 publications

The Metabolism Reprogramming of microRNA Let-7-Mediated Glycolysis Contributes to Autophagy and Tumor Progression

The Metabolism Reprogramming of microRNA Let-7-Mediated Glycolysis Contributes to Autophagy and Tumor Progression

The Dual Role of Autophagy in Cancer Development and a Therapeutic Strategy for Cancer by Targeting Autophagy

Combination of AZD3463 and DZNep Prevents Bone Metastasis of Breast Cancer by Suppressing Akt Signaling

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