Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathway

Chen, Huaqing; Zhu, Tong; Huang, Xiaojie; Xu, Wen-shuang; Di, Zemin; Ma, Yuyang; Xue, Min; Bi, Sixing; Shen, Yujun; Yan, Yu; Shen, Yujun; Feng, Lijie

doi:10.1002/prp2.1041

Cited by 7 publications

(5 citation statements)

References 34 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…None of the treatments for glioma have been able to provide a complete cure. In the case of glioma treatment candidates, recent studies have found that, in addition to the commonly used drug temozolomide, numerous natural drugs such as RA ( 24 ), matrine ( 25 ), xanthatin ( 26 , 47 ), PP7 ( 27 ), Shikonin ( 36 ), PAB ( 68 ), PLB ( 69 ), IBC ( 79 ), Pristimerin ( 94 ), MAM ( 95 ), DPT ( 99 ), etc. inhibit the growth of interlacing and inhibiting glioma by inducing apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, necrosis and parthanayos.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

“…As a serine/threonine kinase, mTOR is a major regulator of cellular metabolism that promotes cell growth in response to environmental signals (46). mTOR exists in two distinct signaling complexes, mTORC1 and mTORC2: (1) mTORC1 integrates nutrient and growth factor signals to facilitate anabolic pathways like protein and lipid synthesis, while also inhibiting catabolic pathways such as lysosomal biogenesis and autophagy; (2) mTORC2 regulates cell survival, metabolism, and cytoskeletal organization through AGC family kinases.…”

Section: Mtormentioning

confidence: 99%

See 1 more Smart Citation

Regulated cell death in glioma: promising targets for natural small-molecule compounds

Han,

Li,

Fan

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

Gliomas are prevalent malignant tumors in adults, which can be categorized as either localized or diffuse gliomas. Glioblastoma is the most aggressive and deadliest form of glioma. Currently, there is no complete cure, and the median survival time is less than one year. The main mechanism of regulated cell death involves organisms coordinating the elimination of damaged cells at risk of tumor transformation or cells hijacked by microorganisms for pathogen replication. This process includes apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, necrosis, parthanayosis, entosis, lysosome-dependent death, NETosis, oxiptosis, alkaliptosis, and disulfidaptosis. The main goal of clinical oncology is to develop therapies that promote the effective elimination of cancer cells by regulating cell death are the main goal of clinical oncology. Recently, scientists have utilized pertinent regulatory factors and natural small-molecule compounds to induce regulated cell death for the treatment of gliomas. By analyzing the PubMed and Web of Science databases, this paper reviews the research progress on the regulation of cell death and the role of natural small-molecule compounds in glioma. The aim is to provide help for the treatment of glioblastoma.

show abstract

Section: Conclusion and Perspectivementioning

confidence: 99%

Section: Mtormentioning

confidence: 99%

Regulated cell death in glioma: promising targets for natural small-molecule compounds

Han,

Li,

Fan

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Given that the PI3K/AKT/mTOR signaling pathway is a well-established negative regulator of autophagy, with active mTOR inhibiting autophagy, the modulation of this pathway can be crucial for autophagy restoration. 34,35 When the PI3K/AKT/mTOR pathway is inhibited, the suppression on autophagy is relieved, potentially leading to increased autophagic activity. Western blot results confirmed that high glucose levels stimulated the phosphorylation of PI3K, AKT, and mTOR proteins in podocytes.…”

Section: Irisin Enhanced Podocyte Autophagy By Inhibiting Abnormal Ac...mentioning

confidence: 99%

Irisin ameliorates diabetic kidney disease by restoring autophagy in podocytes

Lai,

Luo,

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

Many studies have highlighted the importance of moderate exercise. While it can attenuate diabetic kidney disease, its mechanism has remained unclear. The level of myokine irisin in plasma increases during exercise. We found that irisin was decreased in diabetic patients and was closely related to renal function, proteinuria, and podocyte autophagy injury. Muscle‐specific overexpression of PGC‐1α (mPGC‐1α) in a mouse model is known to increase plasma irisin levels. The mPGC‐1α mice were crossed with db/m mice to obtain db/db mPGC‐1α+ mice in the present study. Compared to db/db mice without mPGC‐1α, plasma irisin was increased, and albuminuria and glomerular pathological damage were both alleviated in db/db mPGC‐1α+ mice. Impaired autophagy in podocytes was restored as well. Irisin inhibited the activation of the PI3K/AKT/mTOR signaling pathway in cultured human podocytes and improved damaged autophagy induced by high glucose levels. Then, db/db mice were treated with recombinant irisin, which had similar beneficial effects on the kidney as those in db/db mPGC‐1α+ mice, with alleviated glomerular injury and albuminuria. Moreover, the autophagy in podocytes was also significantly restored. These results suggest that irisin secreted by skeletal muscles protects the kidney from diabetes mellitus damage. It also restores autophagy in podocytes by inhibiting the abnormal activation of the PI3K/AKT/mTOR signaling pathway. Thus, irisin may become a new drug for the prevention and treatment of diabetic nephropathy.

show abstract

“…The molecular mechanisms by which the SC inhibited cell growth and induced cell death were investigated by analyzing the expression levels of proteins associated with cell cycle (p53 and p21) as well as apoptosis (p53, BCL-2, Bax, Casp3 and Casp7), respectively, using Western blot analysis, as we have reported [4,8,18]. Pursuant to this goal, protein lysates were isolated from the 48 h SC-treated MDA-MB-231 cells (0.798 mg/mL), and 30 µg of total cell lysates were separated and transferred to PVDF membranes.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Plants extracts can also inhibit the cell proliferation of cancer cells by inducing cell cycle arrest and apoptosis [16]. On the other hand, phytochemical compounds isolated from plant extract can also inhibit the PI3K/Akt or the NF-κB (Phosphatidylinositol 3-kinase/Alpha serine/therionine-protein Kinase, Nuclear Factor-Kappa B) survival signaling pathways, which are commonly dysregulated in cancer cells to promote cell survival [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Molecular Evidence of Breast Cancer Cell Proliferation Inhibition by a Combination of Selected Qatari Medicinal Plants Crude Extracts

Alateyah,

Alsafran,

Usman

et al. 2023

Nutrients

View full text Add to dashboard Cite

Breast cancer (BC) is the most common malignancy, and conventional medicine has failed to establish efficient treatment modalities. Conventional medicine failed due to lack of knowledge of the mechanisms that underpin the onset and metastasis of tumors, as well as resistance to treatment regimen. However, Complementary and Alternative medicine (CAM) modalities are currently drawing the attention of both the public and health professionals. Our study examined the effect of a super-combination (SC) of crude extracts, which were isolated from three selected Qatari medicinal plants, on the proliferation, motility and death of BC cells. Our results revealed that SC attenuated cell growth and caused the cell death of MDA-MB-231 cancer cells when compared to human normal neonatal fibroblast cells. On the other hand, functional assays showed that SC reduced BC cell migration and invasion, respectively. SC-inhibited cell cycle and SC-regulated apoptosis was most likely mediated by p53/p21 pathway and p53-regulated Bax/BCL-2/Caspace-3 pathway. Our ongoing experiments aim to validate these in vitro findings in vivo using a BC-Xenograft mouse model. These findings support our hypothesis that SC inhibited BC cell proliferation and induced apoptosis. These findings lay the foundation for further experiments, aiming to validate SC as an effective chemoprevention and/or chemotherapeutic strategy that can ultimately pave the way towards translational research/clinical trials for the eradication of BC.

show abstract

Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K‐Akt–mTOR pathway

Cited by 7 publications

References 34 publications

Regulated cell death in glioma: promising targets for natural small-molecule compounds

Regulated cell death in glioma: promising targets for natural small-molecule compounds

Irisin ameliorates diabetic kidney disease by restoring autophagy in podocytes

Molecular Evidence of Breast Cancer Cell Proliferation Inhibition by a Combination of Selected Qatari Medicinal Plants Crude Extracts

Contact Info

Product

Resources

About