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

Ammoury, Carl; Younes, Maria; Khoury, Marianne El; Hodroj, Mohammad Hassan; Haykal, Tony; Nasr, Peter; Sily, Marilyne; Taleb, Robin I.; Naveiras, Olaia; Khalife, Rana; Rizk, Sandra

doi:10.1186/s12906-019-2768-1

Cited by 34 publications

(25 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Caspase-3 is known as the primary executioner of the family that plays a vital function in reaching apoptotic cell death by cleaving the cellular substrates(Abou-Hashem et al 2019 ). Bax (Bcl-2-associated X protein) is a tumor suppressor gene that can promote cell apoptosis (Ammoury et al 2019 ; Liu et al 2015 ). The expression level of Bax and caspase-3 is a known way to evaluated induced apoptosis mechanism (Deng et al 2017 ).…”

Section: Resultsmentioning

confidence: 99%

HPLC phenolic profile and induction of apoptosis by Linum usitatissimum extract in LNCaP cells by caspase3 and Bax pathways

et al. 2020

View full text Add to dashboard Cite

Linum usitatissimum is a candidate as a remedy to treat prostate problems in some folklore medicines. In this study, we have reported the phenolic and flavonoid constituents, antioxidant activity, and potential of the plant extract against prostate cancer cells. The phenolic and flavonoid compound profile of the extract were established using HPLC analysis. While the total phenolic and flavonoid content (TPC and TFC) were analyzed using classic methods. The antioxidant activity of the extract was also evaluated. MTT assay and flow cytometry technique was used to evaluate antiproliferation activity and induction apoptosis of the plant extract on prostate cancer cells of LNCaP. We also evaluated the gene expression of Bax and caspase-3 using the real-time qPCR assay. HPLC result revealed that L. usitatissimum extract (LUE) was rich in phenolic acids such as gallic, ferulic, and vanillic acid with the amount of 3.56, 2.12, 1.24 μg/g extract respectively. 383.4 mg GAE/g and 47.1 mgRuE/g were calculated for total phenolic and flavonoid content. LUE exhibited radical scavenging activity with IC50 = 19.3 ± 1.1 µg/mL. LUE chelated ferrous ions with IC50 = 121.1 ± 1.3 µg/mL. LUE showed anti-proliferative activity on LNCaP cells with the IC50 values of 8.3, 6.3, and 5.4 μg/mL after 24, 48, and 72 h treatment. LUE also increased cell mortality by inducing apoptosis (15.3–29.8%). The real-time qPCR results exhibited an increase in gene expression of Bax and caspase-3. Our in vitro study demonstrates that L. usitatissimum can be considered as an effective agent to inhibit the growth and invasion the human prostate cancer cells.

show abstract

Section: Resultsmentioning

confidence: 99%

HPLC phenolic profile and induction of apoptosis by Linum usitatissimum extract in LNCaP cells by caspase3 and Bax pathways

et al. 2020

View full text Add to dashboard Cite

show abstract

“…To assess cell proliferation, WST1 assay was performed in conformity with the manufacturer's guide instructions (Roche, Penzberg, Germany) and as previously reported [46][47][48]. The assay is based on using the WST-1 tetrazolium salt that is cleaved to generate formazan dye once mixed with metabolically active cells.…”

Section: In Vitro Cell Proliferation Assaymentioning

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

Self Cite

View full text Add to dashboard Cite

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,...

show abstract

“…They were split every 3 days at a ratio of 1:2. Cell viability was continuously checked using the trypan blue exclusion method [23].…”

Section: Cell Culturementioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Cited by 34 publications

References 54 publications

HPLC phenolic profile and induction of apoptosis by Linum usitatissimum extract in LNCaP cells by caspase3 and Bax pathways

HPLC phenolic profile and induction of apoptosis by Linum usitatissimum extract in LNCaP cells by caspase3 and Bax pathways

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

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

Contact Info

Product

Resources

About