Autophagy induction by the 30–100kDa fraction of areca nut in both normal and malignant cells through reactive oxygen species

Ma, Lin; Hsieh, Wan Fang; Chiang, Wei Fan; Hong, Wen; Hsu, Yu Rung; Cheng, Yon Chi; Chen, Tai Chi; Hsu, Kai Cheng; Lina, Pin Yan; Liu, Shyun Yeu; Liu, Young Chau

doi:10.1016/j.oraloncology.2010.08.002

Cited by 25 publications

(23 citation statements)

References 30 publications

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“…ROS induces autophagy, which in turn functions in reducing oxidative damage [18,19], so the ROS level could be associated with chemoresistance and cancer stem cells [20,21,22]. ANE is reported to induce the ROS in both cancer cells and normal oral epithelial cells [9,23]. It was also reported that ANE could induce autophagic flux through ROS [23].…”

Section: Introductionmentioning

confidence: 99%

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Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling

Huang

Shao

et al. 2017

IJMS

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Chewing areca nut is closely associated with oral squamous cell carcinoma (OSCC). The current study aimed to investigate potential associations between areca nut extract (ANE) and cisplatin toxicity in OSCC cells. OSCC cells (Cal-27 and Scc-9) viability and apoptosis were analyzed after treatment with ANE and/or cisplatin. The expressions of proteins associated with autophagy and the AMP-activated protein kinase (AMPK) signaling network were evaluated. We revealed that advanced OSCC patients with areca nut chewing habits presented higher LC3 expression and poorer prognosis. Reactive oxygen species (ROS)-mediated autophagy was induced after pro-longed treatment of ANE (six days, 3 μg). Cisplatin toxicity (IC50, 48 h) was decreased in OSCC cells after ANE treatment (six days, 3 μg). Cisplatin toxicity could be enhanced by reversed autophagy by pretreatment of 3-methyladenine (3-MA), N-acetyl-l-cysteine (NAC), or Compound C. Cleaved-Poly-(ADP-ribose) polymerase (cl-PARP) and cleaved-caspase 3 (cl-caspase 3) were downregulated in ANE-treated OSCC cells in the presence of cisplatin, which was also reversed by NAC and Compound C. Collectively, ANE could decrease cisplatin toxicity of OSCC by inducing autophagy, which involves the ROS and AMPK/mTOR signaling pathway.

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Section: Introductionmentioning

confidence: 99%

“…ANE is reported to induce the ROS in both cancer cells and normal oral epithelial cells [9,23]. It was also reported that ANE could induce autophagic flux through ROS [23]. Adenosine monophosate-activated protein kinase (AMPK) plays an important role in energy metabolism, which can also be triggered by oxidative stress [24].…”

Section: Introductionmentioning

confidence: 99%

Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling

Huang

Shao

et al. 2017

IJMS

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“…ANE 30-100K, but not arecoline, can also increase LC3-II levels, a phenomenon further enhanced by lysosomal enzyme inhibitors, in both non-tumor oral fibroblasts and esophageal carcinoma CE81T/VGH cells, suggesting ANE 30-100K promotes autophagic flux [46]. In addition to these carcinoma cells and fibroblasts, ANE 30-100K also induce similar autophagic responses in peripheral blood lymphocytes and Jurkat T cells, suggesting ANE 30-100K as an autophagy stimulator in a wide spectrum of distinct cell types [45,46]. We also demonstrate that the autophagy-stimulating activity of ANE of cancers [4,5].…”

Section: Linkage Of An With Autophagymentioning

confidence: 93%

“…Although as introduced earlier, autophagy may suppress cancer initiation and progression through the elimination of dysfunctional mitochondria to prevent the accumulation of detrimental free radical, our previous study reveals that ANE 30-100K itself stimulates an increase of intracellular reactive oxygen species [iROS], which is required for ANE 30-100K-induced autophagy and cytotoxicity [46]. Thus, ANE 30-100K-induced autophagy might be unable to prevent the elevation of iROS effectively.…”

Section: Journal Of Biomedical Sciences Issn 2254-609xmentioning

confidence: 94%

“…Arecoline induces cell shrinkage, caspase-3 activation, peri-nuclear condensation of chromatin, and micronucleation; whereas ANE 30-100K causes swallen morphology, emptiness of cytoplasm, nuclear condensation (without peri-nuclear condensation of chromatin, and micronucleation), accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II (one of the hallmarks of autophagy) and generation of acidic vesicles in oral carcinoma OECM-1 cells [45]. ANE 30-100K, but not arecoline, can also increase LC3-II levels, a phenomenon further enhanced by lysosomal enzyme inhibitors, in both non-tumor oral fibroblasts and esophageal carcinoma CE81T/VGH cells, suggesting ANE 30-100K promotes autophagic flux [46]. In addition to these carcinoma cells and fibroblasts, ANE 30-100K also induce similar autophagic responses in peripheral blood lymphocytes and Jurkat T cells, suggesting ANE 30-100K as an autophagy stimulator in a wide spectrum of distinct cell types [45,46].…”

Section: Linkage Of An With Autophagymentioning

confidence: 99%

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Areca Nut contains both Apoptosis- and Autophagy-inducing Ingredients and its Possible Effects on Cancer Cells

Yen¹

2016

J Biomed Sci

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Autophagy is an evolutionally-conserved catabolic process that degrades damaged organelles, misfolded proteins, and toxic aggregates, reducing oxidative stress. Malfunction of autophagy causes various diseases, including cancer. Autophagy can be either tumor suppressive or promotive. Thus, autophagy modulation is being considered as a new strategy to improve cancer therapy. Areca nut (AN) is a worldwide popular carcinogen and contains apoptosis-inducing ingredients. However, we recently demonstrated that AN may predominantly induce autophagic responses in various types of cells. Furthermore, chronic exposure of cancer cells to this activity generally resulted in increased tolerance against environmental challenges, such as serum starvation, hypoxia, and anti-cancer drugs, through upregulated autophagy activity. We, therefore, propose that AN may have the potential to modulate tumors into an autophagy-addicted manner, raising the possibility of improving cancer therapy through autophagy inhibition especially in AN-addicted users. Autophagy backgroundThere are three major forms of autophagy: macroautophagy, microautophagy, and chaperon-mediated autophagy. Among them, macroautophagy (referred to as autophagy hereafter) has received extensive studies in the past decade. This evolutionarily conserved self-eating process delivers intracellular components to the lysosomal compartment for either recycling or degradation. It is thought that damaged proteins and organelles are degraded by basal levels of autophagy to maintain cellular homeostasis, or on the other hand, autophagy can be vigorously triggered for cells to survive nutrient-limited conditions [1]. Impairment of autophagy is now known to be associated with diseases including cancers [2]. Modulation of autophagy may nowadays represent a new direction for improved cancer therapy, which attracts great interest [3].

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Apoferritin‐Cu(II) Nanoparticles Induce Oncosis in Multidrug‐Resistant Colon Cancer Cells

Xiong,

Lin,

Kou

et al. 2023

Adv Healthcare Materials

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Multidrug resistance (MDR) limits the application of clinical chemotherapeutic drugs. There is an urgent need to develop non‐apoptosis‐inducing agents that circumvent drug resistance. Herein, four therapeutic copper complexes encapsulated in natural nanocarrier apoferritin (AFt‐Cu1‐4) are reported. Although they are isomers, they exhibit significantly different organelle distributions and cell death mechanisms. AFt‐Cu1 and AFt‐Cu3 accumulate in the cytoplasm and induce autophagy, whereas AFt‐Cu2 and AFt‐Cu4 can quickly enter the nucleus and trigger oncosis. Excitedly, AFt‐Cu2 and AFt‐Cu4 show a strong tumor growth inhibition effect in mice models bearing multidrug‐resistant colon xenograft via intravenous injection. To the best of the authors’ knowledge, this is the first example of metal‐based nucleus‐targeted oncosis inducers overcoming multidrug resistance in vivo.

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Autophagy induction by the 30–100kDa fraction of areca nut in both normal and malignant cells through reactive oxygen species

Cited by 25 publications

References 30 publications

Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling

Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling

Areca Nut contains both Apoptosis- and Autophagy-inducing Ingredients and its Possible Effects on Cancer Cells

Apoferritin‐Cu(II) Nanoparticles Induce Oncosis in Multidrug‐Resistant Colon Cancer Cells

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