Dataset Information

Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage.

ABSTRACT:

Background

Temozolomide (TMZ)-based chemotherapy represents an effective way for treating human glioma. However, its clinical application is limited because of its side effects and resistance to standard chemotherapy. Hence, the search for novel chemosensitizers to augment their anticancer efficiency has attracted much attention. Natural borneol (NB) has been identified as a potential chemosensitizer in treating human cancers. However, the synergistic effect and mechanism of NB and TMZ in human glioma have not been investigated yet.

Materials and methods

U251 human glioma cells were cultured, and the cytotoxicity and apoptosis of NB and/or TMZ were examined by MTT assay, flow cytometric analysis and Western blot. Nude mice tumor model was also employed to evaluate the in vivo anticancer effect and mechanism.

Results

The results showed that the combined treatment of NB and TMZ more effectively inhibited human glioma growth via triggering mitochondria-mediated apoptosis in vitro, accompanied by the caspase activation. Combined treatment of NB and TMZ also caused mitochondrial dysfunction through disturbing Bcl-2 family expression. Further investigation revealed that NB enhanced TMZ-induced DNA damage through inducing reactive oxide species (ROS) overproduction. Moreover, glioma tumor xenograft growth in vivo was more effectively inhibited by the combined treatment with NB and TMZ through triggering apoptosis and anti-angiogenesis.

Conclusion

Taken together, our findings validated that the strategy of using NB and TMZ could be a highly efficient way to achieve anticancer synergism.

SUBMITTER: Liu WJ

PROVIDER: S-EPMC6129032 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage.

Liu Wen-Jian WJ Yin Yi-Bo YB Sun Jing-Yi JY Feng Sai S Ma Jin-Kui JK Fu Xiao-Yan XY Hou Ya-Jun YJ Yang Ming-Feng MF Sun Bao-Liang BL Fan Cun-Dong CD

OncoTargets and therapy 20180904

<h4>Background</h4>Temozolomide (TMZ)-based chemotherapy represents an effective way for treating human glioma. However, its clinical application is limited because of its side effects and resistance to standard chemotherapy. Hence, the search for novel chemosensitizers to augment their anticancer efficiency has attracted much attention. Natural borneol (NB) has been identified as a potential chemosensitizer in treating human cancers. However, the synergistic effect and mechanism of NB and TMZ i ...[more]

PMID: 30233204

Similar Datasets

Project description:Astrocytic tumors, including astrocytomas and glioblastomas, are the most common type of primary brain tumors. Treatment for glioblastomas includes radiotherapy, chemotherapy with temozolomide (TMZ) and surgical ablation. Despite certain therapeutic advances, the survival time of patients is no longer than 12-14 months. Cancer cells overexpress the neuronal isoform of nitric oxide synthase (nNOS). In the present study, it was examined whether the nNOS enzyme serves a role in the damage of astrocytoma (U251MG and U138MG) and glioblastoma (U87MG) cells caused by TMZ. First, TMZ (250 µM) triggered an increase in oxidative stress at 2, 48 and 72 h in the U87MG, U251MG and U138MG cell lines, as revealed by 2',7'-dichlorofluorescin-diacetate assay. The drug also reduced cell viability, as measured by MTT assay. U87MG cells presented a more linear decline in cell viability at time-points 2, 48 and 72 h, compared with the U251MG and U138MG cell lines. The peak of oxidative stress occurred at 48 h. To examine the role of NOS enzymes in the cell damage caused by TMZ, N(?)-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) were used. L-NAME increased the cell damage caused by TMZ while reducing the oxidative stress at 48 h. The preferential nNOS inhibitor 7-NI also improved the TMZ effects. It caused a 12.8% decrease in the viability of TMZ-injured cells. Indeed, 7-NI was more effective than L-NAME in restraining the increase in oxidative stress triggered by TMZ. Silencing nNOS with a synthetic small interfering (si)RNA (siRNAnNOShum_4400) increased by 20% the effects of 250 µM of TMZ on cell viability (P<0.05). Hoechst 33342 nuclear staining confirmed that nNOS knock-down enhanced TMZ injury. In conclusion, our data reveal that nNOS enzymes serve a role in the damage produced by TMZ on astrocytoma and glioblastoma cells. RNA interference with nNOS merits further studies in animal models to disclose its potential use in brain tumor anticancer therapy.

Dataset Information

Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage.

Background

Materials and methods

Results

Conclusion

Publications

Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage.

Similar Datasets

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