δ‐Tocotrienol sensitizes and re‐sensitizes ovarian cancer cells to cisplatin via induction of G1 phase cell cycle arrest and ROS/MAPK‐mediated apoptosis

Fontana, Fabrizio; Marzagalli, Monica; Raimondi, Mario; Zuco, Valentina; Zaffaroni, Nadia; Limonta, Patrizia

doi:10.1111/cpr.13111

Cited by 24 publications

(6 citation statements)

References 52 publications

(93 reference statements)

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“…Reactive oxygen species (ROS), production of which mainly occurs during mitochondrial respiration, can be detrimental to cells by inducing excessive oxidative stress [ 30 , 31 ]. To evaluate the role of autophagy in this process, we analyzed ROS levels after treatment with rapamycin or 3-MA under oxidative stress.…”

Section: Resultsmentioning

confidence: 99%

Autophagy in Rat Müller Glial Cells Is Modulated by the Sirtuin 4/AMPK/mTOR Pathway and Induces Apoptosis under Oxidative Stress

Qin

Xie

Cao

et al. 2022

Cells

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Müller glial cells (MGCs) are a group of glial cells in the retina that provide essential support to retinal neurons; however, the understanding of MGC apoptosis and autophagy remains limited. This study was aimed at investigating the role of autophagy in MGCs under normal and oxidative conditions, and identifying the underlying mechanisms. In addition, the sirtuin 4 (SIRT4)-mediated signaling pathway was observed to regulate the autophagic process in MGCs. To assess the effect of autophagy on MGC mitochondrial function and survival, we treated rMC-1 cells—rat-derived Müller glial cells—with rapamycin and 3-methyladenine (3-MA), and found that MGC death was not induced by such treatment, while autophagic dysfunction could increase MGC apoptosis under oxidative stress, as reflected by the expression level of cleaved caspase 3 and PI staining. In addition, the downregulation of autophagy by 3-MA could influence the morphology of the mitochondrial network structure, the mitochondrial membrane potential, and generation of reactive oxygen species (ROS) under oxidative stress. Moreover, SIRT4 depletion enhanced autophagosome formation, as verified by an increase in the LC3 II/I ratio and a decrease in the expression of SQSTM1/p62, and vice versa. The inhibition of AMPK phosphorylation by compound C could reverse these changes in LC3 II/I and SQSTM1/p62 caused by SIRT4 knockdown. Our research concludes that MGCs can endure autophagic dysfunction in the absence of oxidative stress, while the downregulation of autophagy can cause MGCs to become more sensitized to oxidative stress. Simultaneous exposure to oxidative stress and autophagic dysfunction in MGCs can result in a pronounced impairment of cell survival. Mechanically, SIRT4 depletion can activate the autophagic process in MGCs by regulating the AMPK–mTOR signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Autophagy in Rat Müller Glial Cells Is Modulated by the Sirtuin 4/AMPK/mTOR Pathway and Induces Apoptosis under Oxidative Stress

Qin

Xie

Cao

et al. 2022

Cells

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“…Recent studies have shown that JNK signaling can be activated in response to various stimuli, including oxidative stress, apoptosis, irradiation and cytokines ( 21 , 22 ). Here, we set out to verify whether the JNK signaling pathway was activated in colon cancer cells after treated with IATL.…”

Section: Resultsmentioning

confidence: 99%

Isoalantolactone Enhances the Antitumor Activity of Doxorubicin by Inducing Reactive Oxygen Species and DNA Damage

Shao

Zheng

et al. 2022

Front. Oncol.

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Colon cancer is one of the most common cancer in the world. Doxorubicin (DOX) is a classical anti-tumor drug which widely used in treatment of cancers, however, high toxicity limited its further clinical application. Thus, it is urgent to find new drugs with low toxicity and high efficiency to treat colon cancer. Isoalantolactone (IATL), an isomeric sesquiterpene lactone isolated from the plant of inula helenium, has been reported to have anti-cancer activity against a variety of cancer cells. However, the function of IATL in colon cancer remains unclear. Here, we demonstrated that IATL inhibited colon cancer cell growth by increasing cellular reactive oxygen species (ROS) production. Further study showed that ROS accumulation contributed to DNA damage and JNK signaling pathway activation. In addition, we found that IATL markedly enhanced DOX-induced cell cytotoxicity in colon cancer cells. IATL in combination with DOX significantly increased the ROS production, induced DNA damage and activated JNK signaling pathway. Taken together, our data suggested that combined treatment with IATL and DOX may serve as a potential therapeutics for colon cancer.

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“…Previous studies have shown that MAPK pathway and Ras pathway are related to tumor proliferation, migration and cisplatin sensitivity. 35 - 37 TME plays an important role in tumor immunity. 38 TILs, a component of the TME, have been shown to correlate with the overall survival of OC.…”

Section: Discussionmentioning

confidence: 99%

Immune-Related Genes’ Prognostic, Therapeutic and Diagnostic Value in Ovarian Cancer Immune-Related Gene Biomarker in Ovarian Cancer

et al. 2023

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Objectives The abnormal expression of immune-related genes (IRGs) plays an important role in the occurrence and progression of ovarian cancer (OC), which is the main cause of mortality among gynecological cancer patients. This study aims to establish a prognostic risk model and comprehensively analyze the relationship between OC risk score and prognosis, immune cell infiltration (ICI) and therapeutic sensitivity in OC. Methods We retrospectively evaluated the clinicopathological characteristics of consecutive OC patients in the Cancer Genome Atlas (TCGA) database. First, the prognostic risk model was constructed by bioinformatics methods. And then, we systematically assessed model robustness, and correlations between risk score and prognosis, and immune cell infiltration. The ICGC cohort was used to verify the prognostic risk model. Finally, we evaluated their value in the treatment of OC immunotherapy and chemotherapy. Results A total of 10 IRGs were identified to construct the prognostic risk model. Survival analysis revealed that patients in the low-risk group had a better prognosis ( P < .01), and the risk score might be considered an independent predictor for predicting the prognosis. In addition, risk scores and patient clinical information were used to construct clinical nomograms, improving the prediction’s precision. We also explored the relationship between the risk score and ICI, immunotherapy and drug sensitivity. Conclusions Collectively, we identified a novel ten IRGs signature that may be applied as a prognostic predictor of OC, thereby benefiting clinical decision-making and personalized treatment of patients.

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δ‐Tocotrienol sensitizes and re‐sensitizes ovarian cancer cells to cisplatin via induction of G1 phase cell cycle arrest and ROS/MAPK‐mediated apoptosis

Cited by 24 publications

References 52 publications

Autophagy in Rat Müller Glial Cells Is Modulated by the Sirtuin 4/AMPK/mTOR Pathway and Induces Apoptosis under Oxidative Stress

Autophagy in Rat Müller Glial Cells Is Modulated by the Sirtuin 4/AMPK/mTOR Pathway and Induces Apoptosis under Oxidative Stress

Isoalantolactone Enhances the Antitumor Activity of Doxorubicin by Inducing Reactive Oxygen Species and DNA Damage

Immune-Related Genes’ Prognostic, Therapeutic and Diagnostic Value in Ovarian Cancer Immune-Related Gene Biomarker in Ovarian Cancer

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