Autophagy Inhibition to Increase Radiosensitization in Breast Cancer

Liang, Diana H.; El‐Zein, Randa; Dave, Bhuvanesh

doi:10.4172/2155-9619.1000254

Cited by 29 publications

(15 citation statements)

References 63 publications

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“…Recent studies show that radiation can damage DNA, plasma membrane and cellular organelle such as mitochondria and ER and activate several radiation responsive pathways. During periods of cellular stress, the convergence of these pathways promotes autophagy (129). To clarify cross talk between autophagy and intracellular radiation response, we focused on the proteins and molecules that link the intracellular radiation response with autophagy.…”

Section: Resultsmentioning

confidence: 99%

Crosstalk between autophagy and intracellular radiation response (Review)

Wang

Huang

et al. 2016

International Journal of Oncology

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Abstract. Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca 2+ concentration which activate many signaling pathways to modulate autophagy. Herein we review the role of autophagy in radiation therapy and the potent intracellular autophagic triggers induced by radiation. We aim to provide a more theoretical basis of radiation-induced autophagy, and provide novel targets for developing cytotoxic drugs to increase radiosensitivity. Contents1. Introduction 2. The role of autophagy in radiotherapy 3. DNA damage repair and autophagy 4. Mitochondrial damage and autophagy 5. ER stress and autophagy 6. ROS and autophagy 7. Ceramide and autophagy 8. Ca 2+ and autophagy 9. Targeting autophagy for radiotherapy 10. Conclusion IntroductionRadiotherapy is an effective strategy for the treatment of many kinds of cancer to kill or control the malignant tumor cells. However, its benefits have been limited due to radiation resistance. It is imperative to identify new targets and develop cytotoxic drugs to increase radiosensitivity. Radiosensitization has traditionally been performed with agents known to induce apoptosis. However, recent studies demonstrate autophagy induced by radiation also plays an important role in cancer Crosstalk between autophagy and intracellular radiation response (Review)

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Section: Resultsmentioning

confidence: 99%

Crosstalk between autophagy and intracellular radiation response (Review)

Wang

Huang

et al. 2016

International Journal of Oncology

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“…Strong evidence has been collected in the last 20 years which supports a dual role of autophagy in cancer, either in tumor suppression or in tumor promotion, depending on the specific cancer type and the stage . Thus, the complex plethora of phenomena which underlie the cellular autophagic response, has become today a very attractive biochemical target for anti‐cancer therapies, although the fundamental genetic mutations and biochemical processes are, for many cases, not fully elucidated: its modulation was shown to promote (re)sensitization of cancer cells to the applied treatment, either cytotoxic agents (chemotherapy) or radiation therapy, for cases of pancreas, breast and prostate cancers, and gliomas –…”

Section: Introductionmentioning

confidence: 99%

Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action

et al. 2019

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The role of autophagy in cancer is often complex, ranging from tumor-promoting to -suppressing effects. In this study, two novel hybrid molecules were designed, containing a ruthenacarborane fragment conjugated with a known modulator of autophagy, namely a quinoline derivative. The complex closo-[3-(η 6 -p-cymene)-1-(quinolin-8-yl-acetate)-3,1,2-RuC 2 B 9 H 10 ](4) showed a dual mode of action against the LN229 (human glioblastoma) cell line, where it inhibited tumor-promoting autophagy, and strongly inhibited cell proliferation, de facto blocking cellular division. These results, together with the tendency to spontaneously form nanoparticles in aqueous solution, make complex 4 a very promising drug candidate for further studies in vivo, for the treatment of autophagy-prone glioblastomas. [a] Dr. . Results from flow cytometric and fluorescence microscopy analysis, and wound healing assay of MCF-7 cells incubated (72 h) with 3 and 4 at 20 μM. (A) CFSE staining (left panel) and wound healing assay (right panel); (B) AnnV/PI double staining; (C) DAPI-stained cells observed under fluorescence microscope (magnification X200). Arrows indicate apoptotic cells; (D) ApoStat staining; (E) AO staining. Experiments were run in triplicate. One representative example per each experiment is shown. For each staining protocol, the respective control (untreated cells) is also shown. (FL1, green channel; FL2, orange channel; FL3, dark red channel).

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“…There is an established close association between autophagy and cancer, where it has an important role in cell survival and death (7,8). 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).…”

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

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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.

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Autophagy Inhibition to Increase Radiosensitization in Breast Cancer

Cited by 29 publications

References 63 publications

Crosstalk between autophagy and intracellular radiation response (Review)

Crosstalk between autophagy and intracellular radiation response (Review)

Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action

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

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