Inhibition of glioma cell viability by jatrophone via NF-κB down-regulation and apoptosis inhibitor up-regulation

Abstract

IntroductionThe present study evaluated the pro-survival signaling pathway inhibition potential of jatrophone in glioblastoma cells with the intention to develop effective treatment for glioblastoma.Material and methodsChanges in proliferation of cells were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological changes were evaluated by electron microscopy and apoptosis by flow cytometry.ResultsThe proliferative potential of glioma cells showed significant reduction on treatment with jatrophone. The shrinkage and detachment from the flask surface was prominent in glioma cells on treatment with 15 µM jatrophone. Treatment with jatrophone (4.8 µM) for 72 h increased apoptosis in U87MG and A172 cells. The immunocytochemistry showed a significant decrease in the level of intracellular NF-B p65 in glioma cells on treatment with jatrophone. Jatrophone treatment significantly suppressed nuclear NF-B p65/total NF-B p65 in glioma cells. Treatment with jatrophone suppressed levels of survivin, XIAP and Bcl-2 in glioma cells relative to control. The Bax level in glioma cells was enhanced markedly relative to control on treatment with jatrophone. Activation of caspase-9 and -3 in glioma cells was markedly increased on treatment with jatrophone.ConclusionsJatrophone acts as inhibitory agent for glioblastoma cell proliferation and mediator of apoptosis. Therefore, jatrophone can be used as a therapeutic agent for glioblastoma treatment.

Jatrophone: a cytotoxic macrocylic diterpene targeting PI3K/AKT/NF-κB pathway, inducing apoptosis and autophagy in resistant breast cancer cells

“…The NF-κB has a pivotal role as a mediator for various survival signaling pathways associated with the survival and growth of cancer cells [ 56 ], suggesting that jatrophone may exhibit an anti-proliferative effect on resistant breast cancer cells by targeting NF-κB expression. Moreover, this study implied the involvement of NF-kB as a molecular target of jatrophone [ 14 ]. Additionally, studies displayed NF-κB as a transcription factor implicated in the phosphoinositide-3-kinase PI3K/AKT signaling pathway in breast cancer [ 6 , 57 ].…”

“…Moreover, cell cycle arrest induced by chemotherapy was found to be involved in deciding the cancer response to different treatments, whether to increase the sensitivity of cells to treatment or serve as a protective mechanism [ 39 ]. Jatrophone caused cell cycle arrest of cancer cells in various stages depending on the kind of cancer in the majority of trials, and this was generally seen together with the activation of apoptosis [ 14 , 15 ].…”

“…Nevertheless, a panel of cancer cell lines representing a range of cancers, including lymphocytic leukaemia, cervical, prostate, and colon cancer, were tested against various fractions of Jatropha species [ 9 – 12 ]. It should be noted that only a small number of studies on JA itself have demonstrated its anticancer activity in vitro against hepatocellular cancerous cells [ 13 ], glioma [ 14 ] and triple-negative breast cancer [ 15 ], and the mechanism of this activity is still elusive and undefined.…”