The strategy for enhancing temozolomide against malignant glioma

Nakada, Mitsutoshi; Furuta, Takeshi; Hayashi, Yutaka; Minamoto, Toshinari; Hamada, Jun-ichiro

doi:10.3389/fonc.2012.00098

Cited by 55 publications

(49 citation statements)

References 38 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has also been reported that Res sensitizes GBM tumor initiating cells to radiotherapy by inhibition of STAT3 axis (49)(50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol inhibits glioma cell growth via targeting oncogenic microRNAs and multiple signaling pathways

Wang¹,

Dai

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Resveratrol (Res), a natural polyphenolic compound, has anticancer activity in a variety of cancers. In the present study, the antitumor effect and underlying molecular mechanism of Res on rat C6 glioma growth was studied. The results demonstrated that Res inhibited glioma cell proliferation, arrested cell cycle in S phase and induced apoptosis in vitro. Res also suppressed intracranial C6 tumor growth in vivo and prolonged survival in a fraction of the rats bearing intracranial gliomas. Res significantltly downregulated the specific miRs, including miR-21, miR-30a-5p and miR-19, which have been identified as oncomiRs in our previous studies, and altered the expression of their targeting and crucial genes for glioma formation and progression such as p53, PTEN, EGFR, STAT3, COX-2, NF-κB and PI3K/AKT/mTOR pathway. Therefore, the anti-glioma effect of Res, at least in part, is through the regulation of oncogenic miRNAs. The effect of Res on noncoding RNAs should be studied further. Res is a potential multi-targeting drug for the treatment of gliomas. IntroductionMalignant gliomas are the most common and highly aggressive primary brain tumors. Even using multiple modalities of treatment, including maximal safe resection, radiotherapy, and chemotherapy, the prognosis of patients with malignant gliomas remains dismal (1,2). Therefore, novel therapeutic strategies and drugs for treatment of malignant gliomas are urgently required.A large number of chemopreventive and chemotherapeutic agents have been discovered from natural products and provided promising approaches to treat and prevent cancer (3,4). Res (3,5,4'-trihydroxy-trans-stilbene), a naturally polyphenolic compound, has been identified in the skin of red grapes, peanuts and various food products. It has a variety of important biological effects such as suppression of platelet aggregation, anti-inflammatory, anti-oxidant, and vasorelaxant activities (5-7). Res also exhibits antitumor properties by blocking the three stages of carcinogenesis, initiation, promotion and progression (8). Res has exerted anticancer effects against prostate, breast, leukemia and other epithelial cancer cells. There are some reports on the studies of the treatment of gliomas with Res (9-12) but the molecular mechanism of its antitumorigenic or chemopreventive activities is complex and not fully understood.The objective of the present study was to investigate the anti-proliferative effect of Res on glioma cells using both in vitro and in vivo models. It is well known that small non-coding regulatory RNAs -microRNAs (miRs) are found to be dysregulated in almost all types of cancers and play important roles in cancer development and progression (13)(14)(15)(16)(17). Recent studies have demonstrated that miRs can be regulated by natural agents such as curcumin and Res resulting in suppression of tumor growth, drug resistance and metastasis (18-21). Our previous studies have confirmed that specific miRs, including miR-21, miR19 and miR-30a-5p are upregulated in GBMs with significa...

show abstract

“…It has also been reported that Res sensitizes GBM tumor initiating cells to radiotherapy by inhibition of STAT3 axis (49)(50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol inhibits glioma cell growth via targeting oncogenic microRNAs and multiple signaling pathways

Wang¹,

Dai

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al, 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al, 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al, 2012).…”

Section: Mechanisms Of Resistance To Temozolomide In Glioblastomasmentioning

confidence: 99%

Tumor Suppressor WWOX and p53 Alterations and Drug Resistance in Glioblastomas

Chiang¹,

Chou²,

Wang³

et al. 2013

Front. Oncol.

View full text Add to dashboard Cite

Tumor suppressor p53 are frequently mutated in glioblastomas (GBMs) and appears to contribute, in part, to resistance to temozolomide (TMZ) and therapeutic drugs. WW domain-containing oxidoreductase WWOX (FOR or WOX1) is a proapoptotic protein and is considered as a tumor suppressor. Loss of WWOX gene expression is frequently seen in malignant cancer cells due to promoter hypermethylation, genetic alterations, and translational blockade. Intriguingly, ectopic expression of wild type WWOX preferentially induces apoptosis in human glioblastoma cells harboring mutant p53. WWOX is known to physically bind and stabilize wild type p53. Here, we provide an overview for the updated knowledge in p53 and WWOX, and postulate potential scenarios that wild type and mutant p53, or isoforms, modulate the apoptotic function of WWOX. We propose that triggering WWOX activation by therapeutic drugs under p53 functional deficiency is needed to overcome TMZ resistance and induce GBM cell death.

show abstract

“…This means that other factors, which are currently not known, are probably involved in GBM resistance. The precise mechanism of cell death triggered by TMZ, is still subject to controversial discussion and studies of the association of TMZ with other drugs indeed revealed a complex array of mechanisms implicated in TMZ cytotoxicity [5]. It has been reported that TMZ through the production of O 6 -methylguanine was inducing apoptosis [6].…”

Section: Introductionmentioning

confidence: 99%

Bak and Mcl-1 are essential for Temozolomide induced cell death in human glioma

et al. 2014

View full text Add to dashboard Cite

Temozolomide (TMZ) is an alkylating agent used for the treatment of glioblastoma multiforme (GBM), the main form of human brain tumours in adults. It has been reported that TMZ induced DNA lesions that subsequently trigger cell death but the actual mechanisms involved in the process are still unclear. We investigated the implication of major proteins of the Bcl-2 family in TMZ-induced cell death in GBM cell lines at concentrations closed to that reached in the brain during the treatments. We did not observe modulation of autophagy at these concentrations but we found an induction of apoptosis. Using RNA interference, we showed that TMZ induced apoptosis is dependent on the pro-apoptotic protein Bak but independent of the pro-apoptotic protein Bax. Apoptosis was not enhanced by ABT-737, an inhibitor of Bcl-2/Bcl-Xl/Bcl-W but not Mcl-1. The knock-down of Mcl-1 expression increased TMZ induced apoptosis. Our results identify a Mcl-1/Bak axis for TMZ induced apoptosis in GBM and thus unravel a target to overcome therapeutic resistance toward TMZ.

show abstract

The strategy for enhancing temozolomide against malignant glioma

Cited by 55 publications

References 38 publications

Resveratrol inhibits glioma cell growth via targeting oncogenic microRNAs and multiple signaling pathways

Resveratrol inhibits glioma cell growth via targeting oncogenic microRNAs and multiple signaling pathways

Tumor Suppressor WWOX and p53 Alterations and Drug Resistance in Glioblastomas

Bak and Mcl-1 are essential for Temozolomide induced cell death in human glioma

Contact Info

Product

Resources

About