The Vitamin E Derivative Gamma Tocotrienol Promotes Anti-Tumor Effects in Acute Myeloid Leukemia Cell Lines

Ghanem, Paola; Zouein, Annalise; Mohamad, Maya; Hodroj, Mohammad Hassan; Haykal, Tony; Najem, Sonia Abou; Naim, Hassan Y.; Rizk, Sandra

doi:10.3390/nu11112808

Cited by 22 publications

(19 citation statements)

References 22 publications

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“…Cells were extracted and lysed with incubation buffer, using the Cell Death ELISA kit (Roche), before isolation of fragmented cytosolic DNA. The procedure was then completed as previously described by Ghanem et al [36]…”

Section: Methodsmentioning

confidence: 99%

The pro-apoptotic effect of a Terpene-rich Annona cherimola leaf extract on leukemic cell lines

Ammoury

Younes

Khoury

et al. 2019

BMC Complement Altern Med

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BackgroundThe edible fruit Annona cherimola has previously shown many nutritional and medicinal properties. The current study evaluates the anti-cancer and anti-proliferative properties of Annona cherimola ethanolic leaf extract (AELE) on Acute Myeloid Leukemia (AML) cell lines cultured in vitro (Monomac-1 and KG-1).MethodsThe anti-proliferative effect of A. cherimola ethanolic leaf extract was evaluated via cell viability assay. Its pro-apoptotic effect was assessed through Cell Death ELISA and dual Annexin V/PI staining. To further investigate the molecular mechanism by which the extract promoted apoptosis and inhibited the proliferation of the AML cells used, apoptotic protein expression was determined through western blots. Extract composition was elucidated by Gas Chromatography-Mass Spectrometry (GC-MS).ResultsOur results showed that the treatment with A. cherimola ethanolic leaf extract exhibited an inhibitory effect on the proliferation of both cancer cell lines used in a dose- and time-dependent manner, with no toxic effects on normal mononuclear cells (MNCs) isolated from human bone marrow. This effect was mediated by DNA fragmentation and apoptosis, as revealed by Cell Death ELISA and dual Annexin V/PI staining. Western blot analysis revealed a Bax/Bcl2 dependent mechanism of apoptosis, as well as PARP cleavage, confirming the apoptotic results observed previously. These effects may be attributed to the presence of terpenes which constitute a large component of the leafy extract, as revealed via GC-MS.ConclusionAll the data presented in our study show that the terpene-rich A. cherimola ethanolic leaf extract exhibits an anti-proliferative and pro-apoptotic effect on the AML cell lines used.

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Section: Methodsmentioning

confidence: 99%

The pro-apoptotic effect of a Terpene-rich Annona cherimola leaf extract on leukemic cell lines

Ammoury

Younes

Khoury

et al. 2019

BMC Complement Altern Med

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“…Untreated cells were used as controls. Cells were collected and centrifuged after 48 and 72 h of treatment, and the pellets were stained with both annexin V and PI (annexin V-fluorescein isothiocyanate (FITC) Apoptosis Detection Kit, Abcam, Cambridge, UK) and immediately analyzed using the Accuri C6 flow cytometer, as previously described [26,27]. Upon apoptosis induction, phosphatidyl serine is translocated to the outer leaflet of the cell membrane, and living cells exclude PI from the cytoplasm.…”

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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“…In the last decades, literature is focusing on the importance of tocotrienols especially with several data showing superiority of tocotrienols as antioxidants compared to tocopherols [19,20], in addition to their role as anti-inflammatory [21,22], hypoglycemic [23], immuno-stimulatory [1], cardio- [24,25], hepato- [26], neuro- [27] and nephro-protective agents [28]. Moreover, many anti-cancer effects of tocotrienols have been documented in vitro and in vivo involving proliferation, metastasis, apoptosis and angiogenesis pathways [29,30].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Studies on tocotrienols have progressively revealed the benefits of these vitamin E isoforms on human health. Beta-tocotrienol (beta-T3) is known to be less available in nature compared to other vitamin E members, which may explain the restricted number of studies on beta-T3. In the present study, we aim to investigate the anti-proliferative effects and the pro-apoptotic mechanisms of beta-T3 on two human breast adenocarcinoma cell lines MDA-MB-231 and MCF7. To assess cell viability, both cell lines were incubated for 24 and 48 h, with different concentrations of beta-T3 and gamma-T3, the latter being a widely studied vitamin E isoform with potent anti-cancerous properties. Cell cycle progression and apoptosis induction upon treatment with various concentrations of the beta-T3 isoform were assessed. The effect of beta-T3 on the expression level of several apoptosis-related proteins p53, cytochrome C, cleaved-PARP-1, Bax, Bcl-2, and caspase-3, in addition to key cell survival proteins p-PI3K and p-GSK-3 α/β was determined using western blot analysis. Beta-tocotrienol exhibited a significantly more potent anti-proliferative effect than gamma-tocotrienol on both cell lines regardless of their hormonal receptor status. Beta-T3 induced a mild G1 arrest on both cell lines, and triggered a mitochondrial stress-mediated apoptotic response in MDA-MB-231 cells. Mechanistically, beta-T3 s anti-neoplastic activity involved the downregulation of phosphorylated PI3K and GSK-3 cell survival proteins. These findings suggest that vitamin E beta-T3 should be considered as a promising anti-cancer agent, more effective than gamma-T3 for treating human breast cancer and deserves to be further studied to investigate its effects in vitro and on other cancer types. Figure 4. Beta-tocotrienol induced a cell cycle arrest of ER-(+ve) MCF7 cells. Cell cycle distribution 267 was assessed by flow cytometry after propidium iodide staining using the range of concentrations: 0-268 50 μM for 24 (A) or 48 h (B). Figures (A) and (B) were obtained by the C Flow software. (C) and (D) 269 represent histograms for analysis of the percentages of cells in each cell cycle phase upon treatment 270 with beta-T3 for 24 and 48 h respectively. *, ** and *** indicate p < 0.05, p < 0.001 and p < 0.0001 271 respectively.272 3.3. Beta-Tocotrienol Induces Apoptosis in BC Cell Lines 273 Due to the observed decrease in cellular proliferation and the increase in sub-G1 population, 274 dual Annexin V/PI staining was performed on both MDA-MB-231 and MCF7 cells treated with beta 275 vitamin E isomer for 24 and 48 h, to examine the tocotrienol potential pro-apoptotic effects. Cells 276 were then analyzed using flow cytometry. Figures 5 and 6 revealed that beta-T3 triggered a dose-277 and time-dependent elevation in the apoptotic percentages of both BC cell lines. 278 279 280 Author Contributions: Conceptualization, S.R.; methodology, S.R.; performing experiments and investigation, M.I.; formal analysis, M.I. and M.H.H.; resources, S.R.; writing-original draft preparation,...

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The Vitamin E Derivative Gamma Tocotrienol Promotes Anti-Tumor Effects in Acute Myeloid Leukemia Cell Lines

Cited by 22 publications

References 22 publications

The pro-apoptotic effect of a Terpene-rich Annona cherimola leaf extract on leukemic cell lines

The pro-apoptotic effect of a Terpene-rich Annona cherimola leaf extract on leukemic cell lines

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

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

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