Taxifolin Targets PI3K and mTOR and Inhibits Glioblastoma Multiforme

Yao, Weiqi; Gong, Hongyun; Mei, Heng; Shi, Lei; Yu, Jinming; Hu, Yu

doi:10.1155/2021/5560915

Cited by 12 publications

(2 citation statements)

References 65 publications

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“…It has been found that taxifolin have effect of treatment on primary malignant brain tumor by inhibited mTOR/PI3K, promoted autophagy and suppressed lipid synthesis in GBM [ 35 ]. In addition, taxifolin also have a cardioprotective effect on diabetes cardiomyopathy by inhibiting oxidative stress and cardiomyocyte apoptosis [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Potential of Tamarind Shell Extract against Oxidative Stress In Vivo and In Vitro

Huang

Han

et al. 2023

Molecules

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Tamarind shell is rich in flavonoids and exhibits good biological activities. In this study, we aimed to analyze the chemical composition of tamarind shell extract (TSE), and to investigate antioxidant capacity of TSE in vitro and in vivo. The tamarind shells were extracted with 95% ethanol refluxing extraction, and chemical constituents were determined by ultra-performance chromatography–electrospray tandem mass spectrometry (UPLC-MS/MS). The free radical scavenging activity of TSE in vitro was evaluated using the oxygen radical absorbance capacity (ORAC) method. The antioxidative effects of TSE were further assessed in 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH)-stimulated ADTC5 cells and tert-butyl hydroperoxide (t-BHP)-exposed zebrafish. A total of eight flavonoids were detected in TSE, including (+)-catechin, taxifolin, myricetin, eriodictyol, luteolin, morin, apigenin, and naringenin, with the contents of 5.287, 8.419, 4.042, 6.583, 3.421, 4.651, 0.2027, and 0.6234 mg/g, respectively. The ORAC assay revealed TSE and these flavonoids had strong free radical scavenging activity in vitro. In addition, TSE significantly decreased the ROS and MDA levels but restored the SOD activity in AAPH-treated ATDC5 cells and t-BHP-exposed zebrafish. The flavonoids also showed excellent antioxidative activities against oxidative damage in ATDC5 cells and zebrafish. Overall, the study suggests the free radical scavenging capacity and antioxidant potential of TSE and its primary flavonoids in vitro and in vivo and will provide a theoretical basis for the development and utilization of tamarind shell.

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Section: Discussionmentioning

confidence: 99%

Potential of Tamarind Shell Extract against Oxidative Stress In Vivo and In Vitro

Huang

Han

et al. 2023

Molecules

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“…This results in the suppression of apoptosis. Subsequently, activated Akt by mediating protein synthesis activates mTOR (downstream target of PI3K) [ 92 ]. Hyperactivation of the PI3K/Akt pathway in GBM induces both the rapid growth of tumors and multidrug resistance.…”

Section: Main Pharmacological Options In the Treatment Of Glioblastomamentioning

confidence: 99%

New Directions in the Therapy of Glioblastoma

Szklener

Mazurek²,

Wieteska³

et al. 2022

Cancers

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Glioblastoma is the most common histologic type of all gliomas and contributes to 57.3% of all cases. Despite the standard management based on surgical resection and radiotherapy, it is related to poor outcome, with a 5-year relative survival rate below 6.9%. In order to improve the overall outcome for patients, the new therapeutic strategies are needed. Herein, we describe the current state of knowledge on novel targeted therapies in glioblastoma. Based on recent studies, we compared treatment efficacy measured by overall survival and progression-free survival in patients treated with selected potential antitumor drugs. The results of the application of the analyzed inhibitors are highly variable despite the encouraging conclusions of previous preclinical studies. This paper focused on drugs that target major glioblastoma kinases. As far, the results of some BRAF inhibitors are favorable. Vemurafenib demonstrated a long-term efficacy in clinical trials while the combination of dabrafenib and trametinib improves PFS compared with both vemurafenib and dabrafenib alone. There is no evidence that any MEK inhibitor is effective in monotherapy. According to the current state of knowledge, BRAF and MEK inhibition are more advantageous than BRAF inhibitor monotherapy. Moreover, mTOR inhibitors (especially paxalisib) may be considered a particularly important group. Everolimus demonstrated a partial response in a significant proportion of patients when combined with bevacizumab, however its actual role in the treatment is unclear. Neither nintedanib nor pemigatinib were efficient in treatment of GBM. Among the anti-VEGF drugs, bevacizumab monotherapy was a well-tolerated option, significantly associated with anti-GBM activity in patients with recurrent GBM. The efficacy of aflibercept and pazopanib in monotherapy has not been demonstrated. Apatinib has been proven to be effective and tolerable by a single clinical trial, but more research is needed. Lenvatinib is under trial. Finally, promising results from a study with regorafenib may be confirmed by the ongoing randomized AGILE trial. The studies conducted so far have provided a relatively wide range of drugs, which are at least well tolerated and demonstrated some efficacy in the randomized clinical trials. The comprehensive understanding of the molecular biology of gliomas promises to further improve the treatment outcomes of patients.

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