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

• Published in: Oncology reports Vol. 31; no. 1; pp. 248 - 254
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.01.2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Antibiotics; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy (Cytology); Autophagy - drug effects; Cancer therapies; Cell cycle; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Cytoplasm; Drug therapy; Experiments; Gene Deletion; Health aspects; Humans; low-dose cisplatin; Lung cancer; Lung Neoplasms - metabolism; Metabolism; Microtubule-Associated Proteins - biosynthesis; p53; Patient outcomes; Proteins; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - physiology; Tumorigenesis; Tumors; United States > US
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2013.2809

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.