Himachalol induces apoptosis in B16-F10 murine melanoma cells and protects against skin carcinogenesis

Shebaby, Wassim N.; Elias, Andree; Mroueh, Mohamad; Nehme, Bilal; Jalbout, Nahia Dib El; Iskandar, Rita; Daher, Joey C.; Zgheib, Michelle; Ibrahim, Pascale; Dwairi, Vanessa; Saad, Jean Michel; Taleb, Robin I.; Daher, Costantine F.

doi:10.1016/j.jep.2020.112545

Cited by 19 publications

(17 citation statements)

References 45 publications

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“…The inhibition of the heat shock protein 90/PI3K signaling pathway has been previously associated with reduced melanoma growth (41). Furthermore, the treatment with himachalol significantly promoted skin carcinogenesis cell apoptosis and cell cycle arrest in skin carcinogenesis cells through inhibiting the PI3K/AKT signaling pathway (42). Additionally, Riquelme et al (43) identified a decrease in gastric cancer cell migration and invasion following miR-451a mimic transfection, which was achieved by the regulation of the PI3K/AKT/mTOR axis.…”

Section: Discussionmentioning

confidence: 94%

MicroRNA‑451a prevents cutaneous squamous cell carcinoma progression via the 3‑phosphoinositide‑dependent protein kinase‑1‑mediated PI3K/AKT signaling pathway

Zhao

Zhang

et al. 2020

Exp Ther Med

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The role of microRNAs (miRNAs/miRs) in governing the progression of cutaneous squamous cell carcinoma (cSCC) has been the focus of recent studies. However, the functional role of miR-451a in cSCC growth remains poorly understood. Therefore, the present study aimed to determine the expression levels of miR-451a in cSCC cell lines and the involvement of miR-451a in cSCC progression. The results revealed that the expression levels of miR-451a were downregulated in cSCC tissues and cell lines, and that this subsequently upregulated 3-phosphoinositide-dependent protein kinase-1 (PDPK1) expression levels. PDPK1 was validated as a direct target of miR-451a in cSCC using bioinformatics software Starbase, dual-luciferase reporter gene assays and western blotting. Additionally, CCK-8, EdU and Transwell assays, as well as flow cytometry and Hoechst 3325 staining, were performed to assess the malignant aggressiveness of cSCC cells. Overexpression of miR-451a was demonstrated to impair the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and promoted apoptosis in cSCC cells by interacting with PDPK1, possibly by direct targeting. Furthermore, the western blotting results indicated that miR-451a overexpression may block the PI3K/AKT signaling pathway by interacting with PDPK1. In conclusion, the findings of the present study suggested that miR-451a may prevent the proliferation, migration, invasion and EMT of cSCC cells through the PDPK1-mediated PI3K/AKT signaling pathway, which may offer potential therapeutic targets for the treatment of cSCC.

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Section: Discussionmentioning

confidence: 94%

MicroRNA‑451a prevents cutaneous squamous cell carcinoma progression via the 3‑phosphoinositide‑dependent protein kinase‑1‑mediated PI3K/AKT signaling pathway

Zhao

Zhang

et al. 2020

Exp Ther Med

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“…The pellet was resuspended in incubation buffer and stained with Annexin V and propidium iodide (PI) following the manufacturer's instruction (Annexin V-FITC Apoptosis Detection Kit; Abcam). Cells were then analyzed by flow cytometer using the BD Accuri C6 Plus Software as previously described [50,51]. Living cells are stained negative for both Annexin-V and PI.…”

Section: Cell Apoptosis Detection By Annexin V/pi Stainingmentioning

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 procarcinogenic nature of DMBA is metabolized by phase I enzymes such as cytochrome P450 to 3,4diol-1,2-epoxide, its ultimate carcinogenic metabolite, which covalently binds to DNA and form DNA adducts which cause mutation and carcinogenesis 20 . Oxidative stress caused by Reactive Oxygen Species (ROS) which are generated excessively during the metabolic activation of DMBA, contributes to the pathogenesis of cancer 21,22,23 .…”

Section: Discussionmentioning

confidence: 99%

Untitled

2020

IJPSR

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Chemoprevention is the novel approach that inhibits and delays or reverses the process of cancer development by using natural herbs and plant products. The aim of the present study was to evaluate the anticancer efficacy of orally administered Capparis decidua fruit extract (CDE) on skin carcinogenesis model in swiss albino mice by the single topical application of the 7,12 dimethylbenz (a)anthracene (100µg/100µl of acetone) followed by croton oil after 2 weeks (1% in acetone/thrice in a week). Oral administration of the CDE at a dose of 50 mg/kg b.wt./day during the peri initiation stage (one week before DMBA and one week after the application followed by croton oil till the end of the experiment) and post-initiation stage (after 2 weeks DMBA application, from the day of croton oil treatment till the end of the experiment). A significant reduction in the tumor incidence, tumor burden, and a cumulative number of papillomas was observed, along with the increase in the average latent period in mice treated with CDE drugs compared with DMBA/croton oil-treated group III. A significant elevation was seen in the level of the non-enzymatic antioxidant reduced glutathione (GSH), antioxidant enzymes catalase and superoxide dismutase with a reduction in lipid peroxidation (LPO) in the liver and skin of the mice in both the above-mentioned groups in comparison to DMBA+ croton oil-treated group. The results clearly indicate that the CDE has potent chemopreventive efficacy against two-stage skin carcinogenesis, which can be attributed to its antioxidative and antiperoxidative effects. INTRODUCTION: Cancer is one of the most important causes of death in the population after cardiovascular diseases. It is the second leading cause of death in developed countries. Cancer is not a single disease but is a group of many different diseases that all share biological and pathological characteristics.

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Himachalol induces apoptosis in B16-F10 murine melanoma cells and protects against skin carcinogenesis

Cited by 19 publications

References 45 publications

MicroRNA‑451a prevents cutaneous squamous cell carcinoma progression via the 3‑phosphoinositide‑dependent protein kinase‑1‑mediated PI3K/AKT signaling pathway

MicroRNA‑451a prevents cutaneous squamous cell carcinoma progression via the 3‑phosphoinositide‑dependent protein kinase‑1‑mediated PI3K/AKT signaling pathway

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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