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

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 577 ◽  
Author(s):  
Maya Idriss ◽  
Mohammad Hassan Hodroj ◽  
Rajaa Fakhoury ◽  
Sandra Rizk

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.

2018 ◽  
Vol 16 (2) ◽  
pp. 127-137
Author(s):  
Paula Sofia Coutinho Medeiros ◽  
Ana Lúcia Marques Batista de Carvalho ◽  
Cristina Ruano ◽  
Juan Carlos Otero ◽  
Maria Paula Matos Marques

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.


2020 ◽  
Vol 15 (2) ◽  
pp. 165-173
Author(s):  
Elaheh Amini ◽  
Mohammad Nabiuni ◽  
Seyed Bahram Behzad ◽  
Danial Seyfi ◽  
Farhad Eisvand ◽  
...  

Background: Breast carcinoma is a malignant disease that represents the most common non-skin malignancy and a chief reason of cancer death in women. Large interest is growing in the use of natural products for cancer treatment, especially with goal of suppression angiogenesis, tumor cell growth, motility, as well as invasion and metastasis with low/no toxicity. It is evident from recent patents on the anticancer properties of sesquiterpene lactones such as parthenolide. Objective: In this study, using MDA-MB-231 cells of a human breast adenocarcinoma, the effects of aguerin B, as a natural sesquiterpene lactone, has been evaluated, in terms of the expression of metastatic-related genes (Pak-1, Rac-1 and HIF-1α). Methods: Cytotoxicity of aguerin B was tested toward MDA-MB-231 breast tumor cells using MTT. Scratch assay was accomplished to evaluate the tumor cell invasion. To understand the underlying molecular basis, the mRNA expressions were evaluated by real time PCR. Results: It was found that aguerin B significantly inhibited human breast cancer cell growth in vitro (IC50 = 2μg/mL) and this effect was accompanied with a persuasive suppression on metastasis. Our results showed that aguerin B in IC50 concentration down-regulated Rac-1, Pak-1, Hif-1α and Zeb-1 transcriptional levels. Conclusion: Taken together, this study demonstrated that aguerin B possessed potential anti-metastatic effect, suggesting that it may consider as a potential multi target bio compound for treatment of breast metastatic carcinoma.


Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4332
Author(s):  
Nurul Izzati Zulkifli ◽  
Musthahimah Muhamad ◽  
Nur Nadhirah Mohamad Zain ◽  
Wen-Nee Tan ◽  
Noorfatimah Yahaya ◽  
...  

A bottom-up approach for synthesizing silver nanoparticles (AgNPs-GA) phytomediated by Garcinia atroviridis leaf extract is described. Under optimized conditions, the AgNPs-GA were synthesized at a concentration of 0.1 M silver salt and 10% (w/v) leaf extract, 1:4 mixing ratio of reactants, pH 3, temperature 32 °C and 72 h reaction time. The AgNPs-GA were characterized by various analytical techniques and their size was determined to be 5–30 nm. FTIR spectroscopy indicates the role of phenolic functional groups in the reduction of silver ions into AgNPs-GA and in supporting their subsequent stability. The UV-Visible spectrum showed an absorption peak at 450 nm which reflects the surface plasmon resonance (SPR) of AgNPs-GA and further supports the stability of these biosynthesized nanoparticles. SEM, TEM and XRD diffractogram analyses indicate that AgNPs-GA were spherical and face-centered-cubic in shape. This study also describes the efficacy of biosynthesized AgNPs-GA as anti-proliferative agent against human breast cancer cell lines, MCF-7 and MCF-7/TAMR-1. Our findings indicate that AgNPs-GA possess significant anti-proliferative effects against both the MCF-7 and MCF-7/TAMR-1 cell lines, with inhibitory concentration at 50% (IC50 values) of 2.0 and 34.0 µg/mL, respectively, after 72 h of treatment. An induction of apoptosis was evidenced by flow cytometry using Annexin V-FITC and propidium iodide staining. Therefore, AgNPs-GA exhibited its anti-proliferative activity via apoptosis on MCF-7 and MCF-7/TAMR-1 breast cancer cells in vitro. Taken together, the leaf extract from Garcinia atroviridis was found to be highly capable of producing AgNPs-GA with favourable physicochemical and biological properties.


Author(s):  
Philippa D. Darbre ◽  
Roger J. Daly

SynopsisOestrogen regulates the growth of human breast cancer cell lines ZR-75–1, T-47-D and MCF-7 (KO and McGrath). Basal cell growth can be reduced (T-47-D) or eliminated (ZR-75–1) by prior growth in the absence of steroid and phenol red for three weeks, demonstrating that oestrogens can have long-lasting effects on cells in culture (termed “steroid memory”). Effects of oestradiol on different cell biological parameters are described and interaction with other steroids and serum growth factors is discussed. Antioestrogen action in these cell lines is affected by at least five parameters: (1) presence of phenol red, (2) time in culture, (3) cell density, (4) antioestrogen concentration, (5) steroid memory.An in vitro model for loss of oestrogen sensitivity in breast cancer is presented. Both dependent (ZR-75–1) and responsive (T-47-D) cells lose oestrogen sensitivity when deprived of steroid in the long term but show a gradual increase in growth. For ZR-75–1 cells, the effects appear to be clonal but occur at a high frequency (about 1 in 1,000 cells). Parallel alterations in sensitivity to other steroids, antioestrogens and serum growth factors are shown. Molecular markers of this action are described and the results compared with the well-established model for loss of androgen/glucocorticoid sensitivity in SI 15 cells.


2020 ◽  
Vol 15 (2) ◽  
pp. 143-151
Author(s):  
Sumit Bera ◽  
Subhasis Maity ◽  
Balaram Ghosh ◽  
Animesh Ghosh ◽  
Tapan K. Giri

Background: Capsaicin is a pungent component of chili peppers that suppresses the growth of various cancer cell lines including breast cancer. However, it shows extremely low oral bioavailability due to its poor water solubility. Objective: The objective of the present work was to improve the solubility and dissolution rate of capsaicin. Methods: Solid dispersions were prepared by the solvent evaporation method using different molar ratios of capsaicin and urea (1:1, 1:2, and 1:3). Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) study were used to characterize the solid dispersion. Solid dispersions were evaluated for solubility, dissolution rate and in vitro cytotoxicity in breast cancer cell lines. Results: XRD and DSC studies exhibited the reduced crystallinity of a drug in solid dispersion. Phase solubility study shows that the drug solubility increased by increasing carrier concentration. In vitro release study of the solid dispersion showed the faster dissolution of a drug with increasing carrier concentration. Solid dispersion formulation effectively inhibited the growth of MCF-7 human breast cancer and MDA-MB-231 triple negative human breast cancer cells in an MTT assay that measures metabolic activity, but only slightly decreased cell viability when compared to capsaicin alone. Conclusion: The present study demonstrated that solid dispersion of capsaicin in PEG 6000 overcomes the problems related to the poor aqueous solubility of this drug and improving its dissolution rate.


2020 ◽  
Vol 20 (10) ◽  
pp. 1250-1265
Author(s):  
Reza Rezaei ◽  
Simin Janitabar Darzi ◽  
Mahnaz Yazdani

Background: There is a significant dearth of clinical biochemistry researches to evaluate the facility of exploitation of folate targeted radioactive gold-labeled anti-cancer drugs against various cancer cell lines. Objective: The aim of this paper was to develop a gold-based compound with an efficient therapeutic potential against breast cancer. To this end, the synthesis of the 198Au/PAMAM-MPEG-FA composite was considered here. Methods: The radioactive gold (198Au) nanoparticles were encapsulated into Folic acid (FA)-targeted Polyamidoamine dendrimer (PAMAM) modified with Maleimide-Polyethylene glycol Succinimidyl Carboxymethyl ester (MPEG). After that, anticancer assessments of the prepared 198Au/PAMAM-MPEG-FA hybrid mater against breast cancer were investigated. : Further studies were also devised to compare the anticancer capabilities of the 198Au/PAMAM-MPEG-FA composite with the synthesized P-MPEG, 197Au/P-MPEG, 197Au/P-MPEG-FA, 197Au/P-FA and 198Au/P-MPEG-FA conjugates. The prepared drugs were characterized by means of various analytical techniques. The radionuclidic purity of the 198Au/P-MPEG-FA solution was determined using High Purity Germanium (HPGe) spectroscopy and its stability in the presence of human serum was studied. The cell uptake and toxicity of the prepared drugs were evaluated in vitro, and some comparative studies of the toxicity of the drugs were conducted towards the MCF7 (Human breast cancer cell), 4T1 (Mice breast adenocarcinoma cell) and C2C12 (Mice muscle normal cell). Results: The results showed that cell uptake of 198Au/P-MPEG-FA nanoparticles is high in the 4T1 cell line and the order of uptake is as 4T1> MCF7> C2C12. Moreover, of the tested compounds, 198Au/P-MPEG-FA had the highest toxicity towards the cancerous 4T1 and MCF7 in all concentrations after 24, 48 and 72h (P < 0.001). Furthermore, the cytotoxicity of the drugs was concentration-dependent. Conclusion: On the basis of the present research, 198Au/P-MPEG-FA has been proposed as a good candidate for the induction of cell death in breast cancer, although further experimental and clinical investigations are required.


Author(s):  
D. Shanthi ◽  
R. Saravanan

In the present study aqueous extract of Solanum torvum unripe fruits was used to evaluate its cytotoxic effect and anticancer activity through in vitro studies by 3-(4, 5 dimethyl thiazole-2-yl)-2, 5-diphenyl tetrazolium bromide- MTT assay) on Normal VERO cell line and MCF-7 (Human breast adenocarcinoma cell line). Aqueous extracts of Solanum torvum unripe fruits was found to be effective in the prevention of cell proliferation by breast adenocarcinoma cell lines at 1000 µg/ml from the results obtained during 24 hours of incubation.


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