Celastrol induces caspase-dependent apoptosis through ROS/JNK pathway in Saos-2 cells
HUANG Zhi-ping1, SHAO Li-long2, RUAN Yang-ping2
1. Department of Laboratory Medicine, Traditional Chinese Medical Hospital of Zhuji, Zhuji 311800, China;
2. Instruction for Family Planning of Zhuji, Zhuji 311800, China
AIM: To explore the effect of celastrol on apoptosis of Saos-2 cells and its mechanism.METHODS: Saos-2 cells were treated with various concentrations of celastrol, and the cell viability was measured by MTT assay. Apoptosis and reactive oxygen species (ROS) production were determined by flow cytometry. The protein levels of cleaved caspase-9, cleaved caspase-3 and phosphorylated JNK were evaluated by Western blot. RESULTS: The viability of Saos-2 cells was significantly inhibited by celastrol. Celastrol significantly induced apoptosis of Saos-2 cells. Celastrol significantly induced ROS production in the Saos-2 cells. Western blot analysis demonstrated that celastrol significantly increased the protein levels of cleaved caspase-9, cleaved caspase-3 and phosphorylated JNK in the Saos-2 cells. CONCLUSION: Celastrol induces caspase-dependent apoptosis through ROS/JNK pathway in Saos-2 cells.
Rad MP, Fattahi Masoum SH, Layegh P, et al. Primary osteosarcoma of the sternum: a case report and review of the literature[J]. Arch Bone Jt Surg, 2014, 2(4):272-275.
[2]
Ando K, Heymann MF, Stresing V, et al. Current therapeutic strategies and novel approaches in osteosarcoma[J]. Cancers (Basel), 2013, 5(2):591-616.
[3]
Amaral C, Borges M, Melo S, et al. Apoptosis and autophagy in breast cancer cells following exemestane treatment[J]. PLoS One, 2012, 7(8):e42398.
[4]
Raina K, Agarwal C, Wadhwa R, et al. Energy deprivation by silibinin in colorectal cancer cells: a double-edged sword targeting both apoptotic and autophagic machineries[J]. Autophagy, 2013, 9(5):697-713.
[5]
Khan MR, Islam MT, Yazawa T, et al. Muscarinic cholinoceptor-mediated activation of JNK negatively regulates intestinal secretion in mice[J]. J Pharmacol Sci, 2015, 127(1):150-153.
[6]
Venkatesha SH, Astry B, Nanjundaiah SM, et al. Suppression of autoimmune arthritis by Celastrus-derived Celastrol through modulation of pro-inflammatory chemokines[J]. Bioorg Med Chem, 2012, 20(17):5229-5234.
[7]
Chen S, Gu C, Xu C, et al. Celastrol prevents cadmium-induced neuronal cell death via targeting JNK and PTEN-Akt/mTOR network[J]. J Neurochem, 2014, 128(2):256-266.
[8]
Li PP, He W, Yuan PF, et al. Celastrol induces mitochondria-mediated apoptosis in hepatocellular carcinoma bel-7402 cells[J]. Am J Chin Med, 2015, 43(1):137-148.
[9]
Mi C, Shi H, Ma J, et al. Celastrol induces the apoptosis of breast cancer cells and inhibits their invasion via downregulation of MMP-9[J]. Oncol Rep, 2014, 32(6):2527-2532.
[10]
Lo Iacono M, Monica V, Vavalà T, et al. ATF2 contributes to cisplatin resistance in non-small cell lung cancer and celastrol induces cisplatin resensitization through inhibition of JNK/ATF2 pathway[J]. Int J Cancer, 2015, 136(11):2598-2609.
[11]
Li HY, Zhang J, Sun LL, et al. Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells: an in vitro and in vivo study[J]. Cell Death Dis, 2015, 6:e1604.
[12]
Anavi S, Ni Z, Tirosh O, et al. Steatosis-induced proteins adducts with lipid peroxidation products and nuclear electrophilic stress in hepatocytes[J]. Redox Biol, 2015, 4:158-168.
[13]
Gupta S, Goswami P, Biswas J, et al. 6-Hydroxydopamine and lipopolysaccharides induced DNA damage in astrocytes: Involvement of nitric oxide and mitochondria[J]. Mutat Res Genet Toxicol Environ Mutagen, 2015, 778:22-36.
Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications[J]. Drug Resist Updat, 2004,(7):97-110.
[16]
Krajarng A, Imoto M, Tashiro E, et al. Apoptosis induction associated with the ER stress response through up-regulation of JNK in HeLa cells by gambogic acid[J]. BMC Complement Altern Med, 2015, 15:26.
