Reversine Induced Multinucleated Cells, Cell Apoptosis and Autophagy in Human Non-Small Cell Lung Cancer Cells

Lu, Yin-Che; Lee, Ying‐Ray; Liao, Ji-Der; Lin, Chih-Bin; Chen, Yih-Yuan; Chen, Ping-Tzu; Tseng, Ya-Shih

doi:10.1371/journal.pone.0158587

Cited by 31 publications

(37 citation statements)

References 42 publications

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“…At the initial development phase, autophagy functions as a tumor suppressor mechanism (4,5). However, it prompts the malignant progression of tumors in hypoxic microenvironments (6,7).…”

Section: Introductionmentioning

confidence: 99%

Allicin activates autophagic cell death to alleviate the malignant development of thyroid cancer

Xiang

Zhao

et al. 2018

Exp Ther Med

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Abstract. Allicin has been reported to inhibit cancer cell proliferation, induce cell apoptosis and enhance the accumulation of reactive oxygen species. However, it has remained elusive whether allicin improves multidrug resistance in thyroid cancer cells through modulating autophagy. The present study demonstrated that combined use of allicin and cisplatin or carboplatin resulted in an enhanced growth inhibitory effect on SW1736 and HTh-7 cells. Furthermore, treatment with allicin significantly increased SW1736 and HTh-7 cell autophagy. Of note, allicin-induced cell death was largely abolished by 3-methyladenine or chloroquine treatment, suggesting that allicin-induced A549 cell death was dependent on autophagy. Western blot analysis demonstrated that allicin treatment inhibited the activation of Akt, mammalian target of rapamycin and S6. Furthermore, it was demonstrated that combined use of allicin and rapamycin induced more cell death compared with that induced by allicin or rapamycin alone. In conclusion, allicin may serve as an adjunctive therapy for thyroid cancer, as it induces autophagy-dependent cell death even when cancer cells have developed apoptosis resistance.

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“…At the initial development phase, autophagy functions as a tumor suppressor mechanism (4,5). However, it prompts the malignant progression of tumors in hypoxic microenvironments (6,7).…”

Section: Introductionmentioning

confidence: 99%

Allicin activates autophagic cell death to alleviate the malignant development of thyroid cancer

Xiang

Zhao

et al. 2018

Exp Ther Med

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“…Mechanisms involved in the stimulation of apoptosis by reversine include inhibition of Akt/ mTORC1 signaling [88], caspase activation [5, 10, 22, 88], mitochondrial depolarization [22], autophagy [3, 10, 88] and mitotic catastrophe [20, 25, 27]. …”

Section: Discussionmentioning

confidence: 99%

“…We decided to use the 1, 5 and 10 µM range of concentration. Previous studies used reversine within the range of 0.1 to 100 µM on human colon carcinoma [27], thyroid cancer cells [5], breast cancer cells [23], hepatic stellate cells [22], lung cancer cells [10], oral squamous carcinoma [24] and myeloid leukemia [25]. …”

Section: Methodsmentioning

confidence: 99%

“…The purine analog [1-9] and A3 adenosine receptor antagonist [10, 11], reversine (2-(4-morpholinoanilino)-6-cyclohexylaminopurine) reverses differentiation of lineage-committed cells to mesenchymal stem cells (MSCs) allowing them to undergo differentiation into other various lineages [1, 4, 6-10, 12-21]. Reversine has been shown to inhibit cell proliferation [18, 22], to induce cell-cycle arrest at the G2/M phase [1, 3, 22-24], to trigger apoptosis [3, 5, 10, 23-27], to induce cell swelling with polyploidy [1, 9, 23, 27], and to stimulate autophagy [3, 10, 24].…”

Section: Introductionmentioning

confidence: 99%

“…Reversine has been shown to inhibit cell proliferation [18, 22], to induce cell-cycle arrest at the G2/M phase [1, 3, 22-24], to trigger apoptosis [3, 5, 10, 23-27], to induce cell swelling with polyploidy [1, 9, 23, 27], and to stimulate autophagy [3, 10, 24]. …”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Suicidal Erythrocyte Death by Reversine

Jèmaà

Fezai

Läng³

2017

Cell Physiol Biochem

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Background/Aims: The A3 adenosine receptor antagonist reversine (2-(4-morpholinoanilino)-6-cyclohexylaminopurine) influences cellular differentiation, inhibits cell proliferation, induces cell-cycle arrest, triggers apoptosis, causes cell swelling with polyploidy and stimulates autophagy. The effect on apoptosis involves mitochondria and caspases. Erythrocytes are lacking mitochondria but express caspases and are, similar to apoptosis of nucleated cells, able to enter suicidal erythrocyte death or eryptosis. Stimulators of eryptosis include increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), energy depletion and oxidative stress. The present study explored, whether reversine influences eryptosis. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding and cell volume from forward scatter. Measurements were made without or with energy depletion (glucose deprivation for 48 hours), Ca²⁺ loading (30 minutes treatment with 1 µM Ca²⁺ ionophore ionomycin), or oxidative stress (15 min exposure to 0.3 mM tert-butylhydroperoxide). Results: A 48 hours exposure of human erythrocytes to reversine (1-10 µM) did not significantly modify the percentage of annexin-V-binding cells and forward scatter. Energy depletion, Ca²⁺ loading, and oxidative stress were each followed by profound and significant increase of the percentage annexin-V-binding erythrocytes and a significant decrease of forward scatter. The effects of each, Ca²⁺ loading, energy depletion and oxidative stress on annexin-V-binding were significantly blunted in the presence of reversine (1-10 µM). The effect of ionomycin, but not the effects of energy depletion and oxidative stress on forward scatter were again significantly blunted in the presence of reversine (≥1 µM]. Conclusions: Reversine is a powerful inhibitor of cell membrane scrambling following energy depletion, Ca²⁺ loading and oxidative stress.

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Polyploid giant cancer cells: Unrecognized actuators of tumorigenesis, metastasis, and resistance

et al. 2019

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Cancer led to the deaths of more than 9 million people worldwide in 2018, and most of these deaths were due to metastatic tumor burden. While in most cases, we still do not know why cancer is lethal, we know that a total tumor burden of 1 kg—equivalent to one trillion cells—is not compatible with life. While localized disease is curable through surgical removal or radiation, once cancer has spread, it is largely incurable. The inability to cure metastatic cancer lies, at least in part, to the fact that cancer is resistant to all known compounds and anticancer drugs. The source of this resistance remains undefined. In fact, the vast majority of metastatic cancers are resistant to all currently available anticancer therapies, including chemotherapy, hormone therapy, immunotherapy, and systemic radiation. Thus, despite decades—even centuries—of research, metastatic cancer remains lethal and incurable. We present historical and contemporary evidence that the key actuators of this process—of tumorigenesis, metastasis, and therapy resistance—are polyploid giant cancer cells.

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Reversine Induced Multinucleated Cells, Cell Apoptosis and Autophagy in Human Non-Small Cell Lung Cancer Cells

Cited by 31 publications

References 42 publications

Allicin activates autophagic cell death to alleviate the malignant development of thyroid cancer

Allicin activates autophagic cell death to alleviate the malignant development of thyroid cancer

Inhibition of Suicidal Erythrocyte Death by Reversine

Polyploid giant cancer cells: Unrecognized actuators of tumorigenesis, metastasis, and resistance

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