Therapeutics Targeting the Core Apoptotic Machinery

Hamilton, Claudia; Fox, Jennifer; Longley, Daniel B.; Higgins, Catherine

doi:10.3390/cancers13112618

Cited by 15 publications

(11 citation statements)

References 179 publications

(221 reference statements)

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“…These results confirm Zhang's study in which SFN induced apoptosis in GBM cells most likely through a Bad-Bax/Bcl-2-cytochrome C signaling pathway [26]. [30]. The collapse of mitochondrial structural integrity is an early event of the intrinsic apoptotic pathway [31].…”

Section: The Effects Of Sfn On Mitochondrial and Oxidative Statussupporting

confidence: 88%

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Sulforaphane Causes Cell Cycle Arrest and Apoptosis in Human Glioblastoma U87MG and U373MG Cell Lines under Hypoxic Conditions

Sita

Graziosi

Hrelia

et al. 2021

IJMS

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Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor. The median survival rate from diagnosis ranges from 15 to 17 months because the tumor is resistant to most therapeutic strategies. GBM exhibits microvascular hyperplasia and pronounced necrosis triggered by hypoxia. Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has already demonstrated the ability to inhibit cell proliferation, by provoking cell cycle arrest, and leading to apoptosis in many cell lines. In this study, we investigated the antineoplastic effects of SFN [20–80 μM for 48 h] in GBM cells under normoxic and hypoxic conditions. Cell viability assays, flow cytometry, and Western blot results revealed that SFN could induce apoptosis of GBM cells in a dose-dependent manner, under both conditions. In particular, SFN significantly induced caspase 3/7 activation and DNA fragmentation. Moreover, our results demonstrated that SFN suppressed GBM cells proliferation by arresting the cell cycle at the S-phase, also under hypoxic condition, and that these effects may be due in part to its ability to induce oxidative stress by reducing glutathione levels and to increase the phosphorylation of extracellular signal-regulated kinases (ERKs). Overall, we hypothesized that SFN treatment might serve as a potential therapeutic strategy, alone or in combination, against GBM.

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Section: The Effects Of Sfn On Mitochondrial and Oxidative Statussupporting

confidence: 88%

“…Two distinct pathways of apoptotic cell death have been described: the intrinsic mitochondrial-mediated pathway and the extrinsic death receptor (DR)-mediated pathway [30]. The collapse of mitochondrial structural integrity is an early event of the intrinsic apoptotic pathway [31].…”

Section: The Effects Of Sfn On Mitochondrial and Oxidative Statusmentioning

confidence: 99%

Sulforaphane Causes Cell Cycle Arrest and Apoptosis in Human Glioblastoma U87MG and U373MG Cell Lines under Hypoxic Conditions

Sita

Graziosi

Hrelia

et al. 2021

IJMS

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“…Knockdown of MCL -1, using short hairpin RNA, resulted in a more pronounced reduction in proliferation in MCL-1 amplified cell lines compared to non-amplified controls, indicating the functional relevance of this aberration [ 137 ]. In a range of hematological and solid cancers, MCL-1 has been implicated in tumor formation, cell survival, and treatment resistance, including resistance to BCL-XL and BCL-2 targeting [ 137 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 ]. The majority of pre-clinical studies have been conducted in hematological cancers, where a number of MCL-1 inhibitors have shown promising activity [ 162 , 163 , 164 , 165 , 166 ].…”

Section: Targeting the Intrinsic Apoptosis Pathway With Bh3 Mimeticsmentioning

confidence: 99%

Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer

Westaby

Jiménez‐Vacas

Padilha

et al. 2021

Cancers

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Despite major improvements in the management of advanced prostate cancer over the last 20 years, the disease remains invariably fatal, and new effective therapies are required. The development of novel hormonal agents and taxane chemotherapy has improved outcomes, although primary and acquired resistance remains problematic. Inducing cancer cell death via apoptosis has long been an attractive goal in the treatment of cancer. Apoptosis, a form of regulated cell death, is a highly controlled process, split into two main pathways (intrinsic and extrinsic), and is stimulated by a multitude of factors, including cellular and genotoxic stress. Numerous therapeutic strategies targeting the intrinsic apoptosis pathway are in clinical development, and BH3 mimetics have shown promising efficacy for hematological malignancies. Utilizing these agents for solid malignancies has proved more challenging, though efforts are ongoing. Molecular characterization and the development of predictive biomarkers is likely to be critical for patient selection, by identifying tumors with a vulnerability in the intrinsic apoptosis pathway. This review provides an up-to-date overview of cell death and apoptosis, specifically focusing on the intrinsic pathway. It summarizes the latest approaches for targeting the intrinsic apoptosis pathway with BH3 mimetics and discusses how these strategies may be leveraged to treat prostate cancer.

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“…Melanoma cells avoid programmed cell death through the dysregulation of the balance between proapoptotic and antiapoptotic proteins, as well as caspase activity. One of the most promising strategies is the development of new drugs or therapies targeting proteins of the BCL family, caspases, or other mediators involved in apoptosis [ 8 ]. Numerous efforts are being put toward the development of cancer therapeutic strategies with the use of plant-derived compounds [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Pterostilbene-Mediated Inhibition of Cell Proliferation and Cell Death Induction in Amelanotic and Melanotic Melanoma

Wawszczyk

Jesse

Kapral

2023

IJMS

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Melanoma is one of the fastest-growing cancers worldwide. Treatment of advanced melanoma is very difficult; therefore, there is growing interest in the identification of new therapeutic agents. Pterostilbene is a natural stilbene that has been found to have several pharmacological activities. The aim of this study was to evaluate the influence of pterostilbene on the proliferation and apoptosis of human melanoma cells. Proliferation of pterostilbene-treated amelanotic (C32) and melanotic (A2058) melanoma cells was determined by BRDU assay. Flow cytometric analyses were used to determine cell cycle progression, and further molecular investigations were performed using real-time RT-qPCR. The expression of the p21 protein and the DNA fragmentation assay were determined by the ELISA method. The results revealed that pterostilbene reduced the proliferation of both amelanotic and melanotic melanoma cells. Pterostilbene induced apoptosis in amelanotic C32 melanoma cells, and this effect was mediated by an increase in the expression of the BAX, CASP9, and CASP9 genes; induction of caspase 3 activity; and DNA degradation. Pterostilbene did not affect the activation of apoptosis in the A2058 cell line. It may be concluded that pterostilbene has anticancer potential against human melanoma cells; however, more studies are still needed to fully elucidate the effects of pterostilbene on amelanotic and melanotic melanoma cells.

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Therapeutics Targeting the Core Apoptotic Machinery

Cited by 15 publications

References 179 publications

Sulforaphane Causes Cell Cycle Arrest and Apoptosis in Human Glioblastoma U87MG and U373MG Cell Lines under Hypoxic Conditions

Sulforaphane Causes Cell Cycle Arrest and Apoptosis in Human Glioblastoma U87MG and U373MG Cell Lines under Hypoxic Conditions

Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer

Pterostilbene-Mediated Inhibition of Cell Proliferation and Cell Death Induction in Amelanotic and Melanotic Melanoma

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