Autophagy induction by low-dose cisplatin: The role of p53 in autophagy

Cho,Kyung-Hwa; Park,Ji-Hye; Kwon,Kang-Beom; Lee,Young-Rae; So,Hong-Seob; Lee,Kang-Kyoo; Lee,Sam-Youn; Moon,Sun-Rock; Yang,Sei-Hoon

doi:10.3892/or.2013.2809

2014-January Volume 31 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

2014-January Volume 31 Issue 1

Full Size Image

Article

Autophagy induction by low-dose cisplatin: The role of p53 in autophagy

Authors:
- Kyung-Hwa Cho
- Ji-Hye Park
- Kang-Beom Kwon
- Young-Rae Lee
- Hong-Seob So
- Kang-Kyoo Lee
- Sam-Youn Lee
- Sun-Rock Moon
- Sei-Hoon Yang
View Affiliations / Copyright

Affiliations: Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Jeonbuk, Republic of Korea, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk, Republic of Korea, Department of Radiology, Wonkwang University School of Medicine, Iksan, Jeonbuk, Republic of Korea, Department of Thoracic Surgery, Wonkwang University School of Medicine, Iksan, Jeonbuk, Republic of Korea
Pages: 248-254
|
Published online on: October 24, 2013

https://doi.org/10.3892/or.2013.2809
Expand metrics +

Abstract

The majority of chemotherapy treatments for lung cancer use cisplatin; however, its use is limited as it has several side-effects. Autophagy (or type II cell death) is an important mechanism by which programmed cell death occurs. The purpose of this study was to determine whether low-dose cisplatin treatment induces autophagy in lung cancer cells. We also examined whether autophagy inhibition results in p53-mediated apoptosis. NCI-H460 (wild-type p53) and NCI-H1299 (null-type p53) cells were treated with 5 or 20 µM cisplatin for 12, 24 or 48 h. An MTT assay was performed to measure the cell viability following cisplatin treatment. To detect cisplatin-induced autophagy, cell morphology (autophagic vacuole) and LC3 localization were examined. The outcome of autophagy inhibition was determined using 3-methyladenine (3-MA) to detect Annexin V (+), propidium iodide (PI) (-) and acridine orange (+) cells by FACS analysis. To determine whether cisplatin induced autophagy, we examined the role of p53 as a cell survival regulator in autophagy. Low-doses of cisplatin (5 µM) induced cell death and this was augmented by 3-MA in both cell lines. Autophagic vacuoles and cytoplasmic LC3 formation was more evident in H460 cells than in H1299 cells. The induction of autophagy by low-dose cisplatin was increased by 2-fold in H460 compared to H1299 cells. However, the tests for apoptosis showed no difference between the 2 cell lines. Following 3-MA pretreatment, cisplatin-induced autophagy was found to be markedly reduced (a 3-fold reduction) in wild-type p53 compared to null-type p53 cells. However, cisplatin-induced apoptosis increased in wild-type p53 compared to null-type p53 cells. Autophagy induction and apoptotic shift after autophagy inhibition may be mediated by p53 activation in lung cancer cells treated with low-dose cisplatin.

View Figures

View References

1	Ferreira CG, Span SW, Peters GJ, et al: Chemotherapy triggers apoptosis in a caspase-8-dependent and mitochondria-controlled manner in the non-small cell lung cancer cell line NCI-H460. Cancer Res. 60:7133–7141. 2000.PubMed/NCBI
2	Fukuoka M, Yano S, Giaccone G, et al: Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol. 21:2237–2246. 2003. View Article : Google Scholar : PubMed/NCBI
3	Kundu M and Thompson CB: Autophagy: basic principles and relevance to disease. Annu Rev Pathol. 3:427–455. 2008. View Article : Google Scholar : PubMed/NCBI
4	Levine B and Yuan J: Autophagy in cell death: an innocent convict? J Clin Invest. 115:2679–2688. 2005. View Article : Google Scholar : PubMed/NCBI
5	Hara T, Nakamura K, Matsui M, et al: Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 441:885–889. 2006. View Article : Google Scholar : PubMed/NCBI
6	Nakai A, Yamaguchi O, Takeda T, et al: The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med. 13:619–624. 2007. View Article : Google Scholar : PubMed/NCBI
7	Roy S and Debnath J: Autophagy and tumorigenesis. Semin Immunopathol. 32:383–396. 2010. View Article : Google Scholar
8	Kondo Y, Kanzawa T, Sawaya R and Kondo S: The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 5:726–734. 2005. View Article : Google Scholar : PubMed/NCBI
9	Rosenfeldt MT and Ryan KM: The role of autophagy in tumour development and cancer therapy. Expert Rev Mol Med. 11:e362009. View Article : Google Scholar : PubMed/NCBI
10	Giaccia AJ and Kastan MB: The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev. 12:2973–2983. 1998. View Article : Google Scholar : PubMed/NCBI
11	Levine B and Abrams J: p53: the Janus of autophagy? Nat Cell Biol. 10:637–639. 2008. View Article : Google Scholar : PubMed/NCBI
12	Riley T, Sontag E, Chen P and Levine A: Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol. 9:402–412. 2008. View Article : Google Scholar : PubMed/NCBI
13	Zilfou JT and Lowe SW: Tumor suppressive functions of p53. Cold Spring Harb Perspect Biol. 1:a0018832009. View Article : Google Scholar : PubMed/NCBI
14	Green DR and Kroemer G: Cytoplasmic functions of the tumour suppressor p53. Nature. 458:1127–1130. 2009. View Article : Google Scholar : PubMed/NCBI
15	Karantza-Wadsworth V and White E: Role of autophagy in breast cancer. Autophagy. 3:610–613. 2007. View Article : Google Scholar
16	Levine B: Unraveling the role of autophagy in cancer. Autophagy. 2:65–66. 2006. View Article : Google Scholar
17	Morselli E, Galluzzi L, Kepp O, et al: Anti- and pro-tumor functions of autophagy. Biochim Biophys Acta. 1793:1524–1532. 2009. View Article : Google Scholar : PubMed/NCBI
18	Maiuri MC, Tasdemir E, Criollo A, et al: Control of autophagy by oncogenes and tumor suppressor genes. Cell Death Differ. 16:87–93. 2009. View Article : Google Scholar : PubMed/NCBI
19	Vogelstein B, Lane D and Levine AJ: Surfing the p53 network. Nature. 408:307–310. 2000. View Article : Google Scholar : PubMed/NCBI
20	Vousden KH and Lane DP: p53 in health and disease. Nat Rev Mol Cell Biol. 8:275–283. 2007. View Article : Google Scholar
21	Feng Z, Zhang H, Levine AJ and Jin S: The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci USA. 102:8204–8209. 2005. View Article : Google Scholar : PubMed/NCBI
22	Tasdemir E, Maiuri MC and Galluzzi L: Regulation of autophagy by cytoplasmic p53. Nat Cell Biol. 10:676–687. 2008. View Article : Google Scholar : PubMed/NCBI
23	Maiuri MC, Galluzzi L, Morselli E, et al: Autophagy regulation by p53. Curr Opin Cell Biol. 22:181–185. 2010. View Article : Google Scholar

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Autophagy induction by low-dose cisplatin: The role of p53 in autophagy

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Related Articles