Autophagy inhibitor 3-methyladenine potentiates apoptosis induced by dietary tocotrienols in breast cancer cells

Tran, Anh; Ramalinga, Malathi; Kedir, Habib; Clarke, Robert; Kumar, Deepak

doi:10.1007/s00394-014-0707-y

Cited by 47 publications

(30 citation statements)

References 44 publications

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“…1a). These doses correspond to those previously reported for the antitumor activity of tocotrienols in cancer cell lines333435. Strikingly, the same treatment schedule did not affect the growth of human normal melanocytes at both time intervals (Fig.…”

Section: Resultssupporting

confidence: 89%

Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells

Marelli

Marzagalli

Moretti

et al. 2016

Sci Rep

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Malignant melanoma is the leading cause of death from skin cancer. Drug toxicity and resistance represent a serious challange for melanoma treatments. Evidence demonstrates that natural compounds may play a crucial role in cancer prevention, growth and progression. Vitamin E tocotrienols (TT) were shown to possess antitumor activity. Here, we analyzed the effects of δ-TT on melanoma cell growth and the involvement of the endoplasmic reticulum (ER) stress in this activity. The experiments were performed on human melanoma cell lines, BLM and A375. δ-TT exerted a significant proapoptotic effect on both cell lines, involving the intrinsic apoptosis pathway; importantly, this compound did not affect the viability of normal human melanocytes. In melanoma cells, δ-TT exerted its antitumor effect through activation of the PERK/p-eIF2α/ATF4/CHOP, IRE1α and caspase-4 ER stress-related branches. Salubrinal, an inhibitor of the ER stress, counteracted the cytotoxic activity of δ-TT. In vivo experiments performed in nude mice bearing A375 xenografts evidenced that δ-TT reduces tumor volume and tumor mass; importantly, tumor progression was significantly delayed by δ-TT treatment. In conclusion, δ-TT exerts a proapoptotic activity on melanoma cells, through activation of the ER stress-related pathways. δ-TT might represent an effective option for novel chemopreventive/therapeutic strategies for melanoma.

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Section: Resultssupporting

confidence: 89%

Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells

Marelli

Marzagalli

Moretti

et al. 2016

Sci Rep

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“…In addition, a previous study also found that hypoxia and endoplasmic reticulum stress induced by high glucose could activate autophagy as well [19] , which reminds us of the fact that high glucose is an important activator of cell autophagy. Du et al [9] found that 3-MA, which was proved to inhibit autophagy effec- tively [20,21] , could decrease total tube length, the number of branching points, and the average number of migrated cells (from 55 to 20/high-power field) in bovine aortic endothelial cells [9,10] . Our study had the same result showing that 3-MA reduced the number of capillary-like structures and migrated RF/6A cells promoted by high glucose.…”

Section: Discussionmentioning

confidence: 99%

Role of Autophagy in Angiogenesis Induced by a High-Glucose Condition in RF/6A Cells

Li²,

et al. 2017

Ophthalmologica

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Purpose: To study the effect of autophagy on vitality, migration, and tube formation of RF/6A cells under the condition of D-glucose. Methods: Cultured RF/6A cells were randomly divided into 4 groups (control, low glucose, high glucose, and high glucose with 3-methyladenine [3-MA]). Autophagy-related proteins (Atg7, p62, and LC3) were monitored. Cell vitality, cell migration, tube formation, reactive oxygen species (ROS) production, and apoptosis were assessed. Results: Cell vitality significantly decreased and cell migration and tube formation significantly increased in the high-glucose group (p < 0.05). Pretreatment with 3-MA significantly increased cell viability and inhibited cell migration and tube formation (p < 0.05). ROS production increased in the high-glucose group and decreased in the high-glucose with N-acetylcysteine (NAC) group (p < 0.05). The level of apoptosis increased in the high-glucose group, while it was reduced in the high-glucose with 3-MA group. Conclusion: Autophagy maybe participates in the formation of retinal neovascularization induced by high glucose.

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“…3MA blocks autophagy through inhibiting class I and class III phosphatidylinositide-3-kinases (PI3K) [23, 24]. Class III PI3K is a lipid protein that phosphorylates the 3rd position on the inositol ring in phosphatidylinositol to form phosphatidylinositol-3-phosphate (PI3P), which is essential for the initial steps in autophagy [23].…”

Section: Introductionmentioning

confidence: 99%

Autophagy induced by a sulphamoylated estrone analogue contributes to its cytotoxic effect on breast cancer cells

et al. 2016

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Background Autophagy can either be protective and confer survival to stressed cells, or it can contribute to cell death. The antimitotic drug 2-ethyl-3-O-sulpamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) is an in silico-designed 17-β-estradiol analogue that induces both autophagy and apoptosis in cancer cells. The aim of the study was to determine the role of autophagy in ESE-15-ol-exposed human adenocarcinoma breast cancer cells; knowledge that will contribute to future clinical applications of this novel antimitotic compound. By inhibiting autophagy and determining the cytotoxic effects of ESE-15-ol-exposure, deductions could be made as to whether the process may confer resistance to the drug, or alternatively, contribute to the cell death process.Methods and results Spectophometrical analysis via crystal violet staining was used to perform cytotoxicity studies. Morphology studies were done using microscopic techniques namely polarization-optical transmitted light differential interference light microscopy, fluorescent microscopy using monodansylcadaverine staining and transmission electron microscopy. Flow cytometry was used to quantify the autophagy inhibition and assess cell viability. Results obtained indicated that 3-methyladenine inhibited autophagy and increased cell survival in both MCF-7 and MDA-MB-231 cell lines.ConclusionThis in vitro study inferred that autophagy inhibition with 3-methyladenine does not confer increased effectiveness of ESE-15-ol in inducing cell death. Thus it may be concluded that the autophagic process induced by ESE-15-ol exposure in MCF-7 and MDA-MB-231 cells plays a more significant role in cell death than conferring survival.

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Autophagy inhibitor 3-methyladenine potentiates apoptosis induced by dietary tocotrienols in breast cancer cells

Cited by 47 publications

References 44 publications

Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells

Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells

Role of Autophagy in Angiogenesis Induced by a High-Glucose Condition in RF/6A Cells

Autophagy induced by a sulphamoylated estrone analogue contributes to its cytotoxic effect on breast cancer cells

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