Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway

Idriss, Maya; Hodroj, Mohammad Hassan; Fakhoury, Rajaa; Rizk, Sandra

doi:10.3390/biom10040577

Cited by 30 publications

(24 citation statements)

References 85 publications

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“…Upon apoptosis induction, phosphatidyl serine is translocated to the outer leaflet of the cell membrane, and living cells exclude PI from the cytoplasm. Therefore, living cells will stain negative for both FITC-annexin V and PI, whereas those that stain positive for both can be classified as apoptotic dead cells [28].…”

Section: Apoptosis Detectionmentioning

confidence: 99%

Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis

et al. 2020

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Urtica dioica (UD), commonly known as “stinging nettle”, is a herbaceous flowering plant that is a widely used agent in traditional medicine worldwide. Several formulations of UD leaf extract have been reported to exhibit anti-inflammatory and antioxidant properties, with anticancer potential. The current study investigated the possible anticancer properties of nettle tea, prepared from Urtica dioica leaves, on acute myeloid leukemia (AML) cell lines, and deciphered the underlying molecular mechanisms. Treatment of AML cell lines (U-937 and KG-1) with UD aqueous leaf extract resulted in a dose- and time-dependent inhibition of proliferation, an increase in apoptotic hallmarks such as phosphatidylserine flipping to the outer membrane leaflet, and DNA fragmentation as revealed by cell-death ELISA and cell-cycle analysis assays. Apoptosis induction in U937 cells involves alterations in the expression of Bax and Bcl-2 upon exposure to nettle tea. Furthermore, the chemical composition of UD aqueous extract indicated the presence of multiple chemical agents, such as flavonoids and phenolics, mainly patuletin, m/p-hydroxybenzoic acid, and caffeic acid, among others, to which the pro-apoptotic and anti-tumor effects may be attributed.

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Section: Apoptosis Detectionmentioning

confidence: 99%

Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis

et al. 2020

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“…TTs showed significant cytotoxic/pro-apoptotic and metabolism modulatory effects in breast cancer cell lines, including the downregulation of phosphorylated PI3K and GSK-3 cell survival proteins (β-TT), increased mitochondrial stress [ 91 ], ER stress via PERK and pIRE1α signaling, PARP cleavage and caspase-7 activation (γ-TT) [ 92 ], dose-dependent AMPK activation, Akt and mTOR inhibition (γ-TT), the reduction of glycolysis gene expression, glucose utilization, and ATP production (γ-TT) [ 93 , 94 ].…”

Section: Molecular and Cellular Mechanism Of Actionmentioning

confidence: 99%

Vitamin E beyond Its Antioxidant Label

et al. 2021

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Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component.

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“…MDA-MB-231 cells (1.5 × 10 5 cells/mL) were cultured in 6-well plates and incubated overnight. After treatment for 24 h with 261 and 522 μg/mL of AELE and 20 μM topotecan (positive control), the cells were stained with Propidium iodide (PI, Abcam, Cambridge, UK) following fixation with ice-cold absolute ethanol [38]. The Accuri C6 flow cytometer was used to assess their DNA content and were classified as follows: sub-G0/G1 phase cells (Pre-G or dead cells) have <2n, G0/G1 phase cells have 2n, S phase cells have between 2n and 4n, and G2/M phase cells have 4n.…”

Section: Cell Cycle Analysismentioning

confidence: 99%

The selective anti-proliferative and pro-apoptotic effect of A. cherimola on MDA-MB-231 breast cancer cell line

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Ammoury

Haykal

et al. 2020

BMC Complement Med Ther

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Background Herbal medicines have been a major target for numerous studies through the past years as an alternative treatment for cancer, mainly due to their minimal effects on normal healthy cells. Annona cherimola, popularly known as Cherimoya, is an edible natural fruit rich in phytochemical components and known to possess various biological activities. Previous studies have reported the anti-cancerous effect of A. cherimola ethanolic leaf extract (AELE) on leukemia. This study aims at studying the potential anti-cancer activity of this extract in vitro in two different breast cancer cell lines, namely MDA-MB-231 and MCF-7, in addition to investigating its toxicity on normal mesenchymal stem cells. Methods The anti-proliferative effect of AELE was evaluated via cell viability assay. Propidium iodide staining, Cell Death Detection ELISA and flow cytometry analysis of Annexin V binding were used to assess cell cycle progression, DNA fragmentation and apoptosis induction, respectively. Protein expression was determined via Western Blot analysis to decipher the underlying apoptotic molecular mechanism induced upon AELE treatment. Results The anti-proliferative effect of the extract was found to be selective on the triple-negative breast cancer cell line (MDA-MB-231) in a time- and dose-dependent manner with an IC50 of 390.2 μg/mL at 48 h, with no cytotoxic effects on normal murine mesenchymal stem cells. The pro-apoptotic effect was confirmed by the increase in cellular and DNA fragmentation, flipping of the phosphatidylserine moiety to the outer leaflet, and the increase in Annexin V binding. The underlying molecular mechanism revealed the involvement of the mitochondrial pathway, as shown by alterations in mitochondrial permeability and the upregulation of cytochrome c expression. Conclusion All the data presented in our study suggest that AELE exhibits a selective anti-proliferative and pro-apoptotic effect on the chemo-resistant MDA-MB-231 breast cancer cells, providing evidence for the anti-tumor effects of A. cherimola.

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Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway

Cited by 30 publications

References 85 publications

Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis

Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis

Vitamin E beyond Its Antioxidant Label

The selective anti-proliferative and pro-apoptotic effect of A. cherimola on MDA-MB-231 breast cancer cell line

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