Enhanced cytotoxic activity of doxorubicin through the inhibition of autophagy in triple negative breast cancer cell line

Aydınlık, Şeyma; Erkısa, Merve; Cevatemre, Buse; Sarimahmut, Mehmet; Dere, Egemen; Arı, Ferda; Ulukaya, Engin

doi:10.1016/j.bbagen.2016.11.013

Cited by 42 publications

(29 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Autophagy is strongly activated by various stress conditions, including cancer chemotherapy and radiotherapy (9). Certain cytotoxic drugs induce protective autophagy, impairing rather than enhancing the action of the drug (10,11). Recent studies have reported that cisplatin treatment activated autophagy, which served as a survival factor to counter cisplatin-induced apoptosis in other cancer cells (12).…”

Section: Introductionmentioning

confidence: 99%

Cisplatin-induced autophagy protects breast cancer cells from apoptosis by regulating yes-associated protein

Jiang

Liu

et al. 2017

Oncol Rep

View full text Add to dashboard Cite

Breast cancer is a common cause of cancer‑related deaths in women. Treatment with cisplatin exhibits some therapeutic efficacy. However, treatment optimization is required, and the mechanisms underlying the cisplatin's proapoptotic effects remain unclear. In the present study, we demonstrated that cisplatin induced apoptosis and autophagy in breast cancer cells. Autophagy induced by cisplatin played a protective role in breast cancer cells, which impaired its proapoptotic effect. Mechanistically, for the first time, we found that cisplatin treatment activated the MAPK signaling pathway and promoted autophagy via the ERK signaling pathway. Notably, we found that nuclear translocation of yes-associated protein (YAP) was regulated by cisplatin-induced autophagy, and we identified YAP as a survival input that promoted survival in cisplatin-treated breast cancer cells. These findings revealed that administration of cisplatin along with an autophagy inhibitor is a promising therapeutic strategy for treating breast cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Cisplatin-induced autophagy protects breast cancer cells from apoptosis by regulating yes-associated protein

Jiang

Liu

et al. 2017

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…9 DOX, an anticancer drug belongs to anthracycline group, has a broad-spectrum antineoplastic effect and is used for the treatment of various types of cancers and TNBC and in combination with endocrine therapy for luminal breast cancer. 26,27 It has been reported that DOX resistance mainly occurs through increased ABC transporters, epithelial mesenchymal transition, changes in target proteins (topoisomerase II and ERK1/ 2), and overexpression of detoxifying enzymes. 28 Moreover, some studies elucidated that DOX exposure induces autophagic flux that is involved in DOX resistance in a variety of cancer types including osteosarcoma, 29 hepatocellular carcinoma, 30 neuroblastoma, 31 and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Autophagy in Acquired Drug Resistance of Human Breast Cancer Cells MCF7 to Doxorubicin

Amani

Shaki

Shokrzadeh

2019

Applied In Vitro Toxicology

View full text Add to dashboard Cite

Introduction: At present, autophagy has attracted increased attention as a potential therapeutic target for breast cancer. Many investigators are trying to overcome drug resistance by inhibition of autophagy. The development of in vitro drug-resistant cell lines with well-characterized autophagy-related markers is required to discover new autophagy inhibitors. Therefore, in this study we established resistant human breast cancer cells MCF7 to doxorubicin (DOX) and used flow cytometric assays to study autophagic flux. Materials and Methods: Resistant MCF7 subline (MCF7.res) was derived from parental MCF7 cells (MCF7.par) by continuous exposure to stepwise increasing concentrations of DOX (30-54 lM). Autophagic flux was assessed by the antibody labeling of the microtubule-associated protein LC3-II and analyzed by flow cytometry. In addition, lysosomal mass was measured flow cytometrically by LysoTracker Green (LTG) staining. The median fluorescence intensity of anti-LC3-II and LTG was compared between parental and resistant MCF7 cells. For detection of apoptotic cell death, Annexin V/propidium iodide staining was performed. After *6 months, MCF7.res subline was obtained from MCF7.par cells. Results: DOX resistance was confirmed by measurement of fold resistance and growth curve analysis. Our established MCF7.res subline exhibited 7.1-fold resistance to DOX compared with MCF7.par cells. Flow cytometric analysis revealed that LC3-II level and LTG signal were elevated in MCF7.res compared with MCF7.par, elucidating increased autophagic flux. The results of apoptosis assay showed that chloroquine (an autophagy inhibitor) could reverse drug resistance of MCF7.res by inhibiting autophagy. Conclusion: Our established DOX-resistant MCF7 cells model is reliable and applicable for investigating new autophagy inhibitors.

show abstract

“…The AO-F staining method is a kind of unique liquid biopsy technique that has been used in a wide variety of microbiological and oncological fields, including microorganism, parasite, bacteria and tumor cell research (20–23). Duan et al (24) observed that that the AO-F dye was unable to label monodansylcadaverine-labeled autophagic vesicles with rims decorated with light chain 3 (25), an autophagy related lipidation, when nitric oxide was depleted in estrogen receptor-positive MCF7 breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

New applications of the acridine orange fluorescence staining method: Screening for circulating tumor cells

et al. 2017

View full text Add to dashboard Cite

The aim of the present study was to explore use of the acridine orange fluorescence (AO-F) staining method for screening of circulating tumor cells (CTCs) in renal cell carcinoma (RCC) patients. The AO-F positive staining rate of live and dead tumor cells was calculated. The positive staining rate in the live group was 93.4±3.0%, while the dead group failed to emit specific fluorescence. A known number of tumor cells were added to peripheral blood, and the detection sensitivity of the four groups (50, 100, 200 and 500 cells/tube) was 10.2±3.8, 9.2±2.3, 10.8±2.6 and 10.5±1.9%, respectively. The average detection sensitivity of the four groups was 10.16±2.73%. There was a positive correlation between the number of cells that was positively stained with AO-F and the total number cells in the system (χ2=0.959; P<0.001). Subsequently, the AO-F staining method was used to detect positive staining cells in 8 healthy volunteers (control group), and 112 non-metastatic and 27 metastatic RCC patients. The positive staining rate was 13.67% (19/139) in RCC patients, while none of the control group was positive. The AO-F positive staining rate was not significantly different between the metastatic and non-metastatic patients according to age, gender, the pathological pattern, T2/3 (according to the Tumor-Node-Metastasis classification) or Fuhrman grade, while there was a significant difference according to T1. The positive staining rate was 8.93% (10/112) for non-metastatic patients and 33.33% (9/27) for metastatic patients, which showed a significant difference (P<0.05). In 112 non-metastatic and 27 metastatic patients, the positive staining rate was not significantly associated with gender, age, tumor size, the pathological pattern, T classification, Fuhrman grade, the presence of a lesion or metastasis to the lungs. The present study demonstrated that the method of CTC staining with AO-F, which has high reproducibility and specificity, was feasible for identifying CTCs and warrants further study.

show abstract

Enhanced cytotoxic activity of doxorubicin through the inhibition of autophagy in triple negative breast cancer cell line

Cited by 42 publications

References 53 publications

Cisplatin-induced autophagy protects breast cancer cells from apoptosis by regulating yes-associated protein

Cisplatin-induced autophagy protects breast cancer cells from apoptosis by regulating yes-associated protein

Contribution of Autophagy in Acquired Drug Resistance of Human Breast Cancer Cells MCF7 to Doxorubicin

New applications of the acridine orange fluorescence staining method: Screening for circulating tumor cells

Contact Info

Product

Resources

About