Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells
Copyright © 2017 Elsevier GmbH. All rights reserved..
BACKGROUND: Harmine, a β-carboline alkaloid from Peganum harmala, has multiple anti-tumor activities, especially for its folk therapy for digestive system neoplasm. However, the underlying mechanism of harmine on gastric cancer remains unclear.
PURPOSE: To illuminate the potential anti-tumor activity and mechanism of harmine against gastric cancer cells.
METHODS/STUDY DESIGNS: The anti-proliferative activity of harmine in vitro was evaluated by MTT assay. The autophagic activity induced by harmine was assessed using GFP-LC3 transfection. FITC/PI double staining was applied for the apoptosis inspection. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. The potential mechanisms for proteins level in autophagy and apoptosis were analyzed by Western blot.
RESULTS: Harmine exhibited potent effects on both autophagy and apoptosis. Treatment with harmine could enhance dots of GFP-LC3 in cells. Meanwhile, the process had connection with Beclin-1, LC3-II, and p62 by the inhibition of Akt/mTOR/p70S6K signaling. However, high concentration of harmine led to apoptosis characterized by the propidium/Annexin V-positive cell pollution, cell shrunk and the collapse of mitochondrial membrane potential. The regulation of Bcl-2, Bax and the gathering of cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 contributed to the induction of apoptosis. In addition, 10μM LY294002 (a specific inhibitor of PI3K/Akt) combination with 40μM harmine significantly increased the cytotoxicity to the gastric cancer cells and up-regulated both the apoptosis-related protein (cleaved-PARP, cleaved-caspase-3) and autophagy-related protein (Beclin-1, LC3-II, and p62). Adding the inhibitor of autophagy, 3-MA or BafA1, increased the viability of harmine-exposured gastric cancer cells, which confirmed the role of autophagy played in the gastric cancer cell death induced by harmine.
CONCLUSION: Harmine might be a potent inducer of apoptosis and autophagy, which offered evidences to therapy of harmine in gastric carcinoma in the folk medicine.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Phytomedicine : international journal of phytotherapy and phytopharmacology - 28(2017) vom: 15. Mai, Seite 10-18 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Chuan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.08.2017 Date Revised 09.04.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.phymed.2017.02.008 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM271641746 |
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| 100 | 1 | |a Li, Chuan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 14.08.2017 | ||
| 500 | |a Date Revised 09.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 Elsevier GmbH. All rights reserved. | ||
| 520 | |a BACKGROUND: Harmine, a β-carboline alkaloid from Peganum harmala, has multiple anti-tumor activities, especially for its folk therapy for digestive system neoplasm. However, the underlying mechanism of harmine on gastric cancer remains unclear | ||
| 520 | |a PURPOSE: To illuminate the potential anti-tumor activity and mechanism of harmine against gastric cancer cells | ||
| 520 | |a METHODS/STUDY DESIGNS: The anti-proliferative activity of harmine in vitro was evaluated by MTT assay. The autophagic activity induced by harmine was assessed using GFP-LC3 transfection. FITC/PI double staining was applied for the apoptosis inspection. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. The potential mechanisms for proteins level in autophagy and apoptosis were analyzed by Western blot | ||
| 520 | |a RESULTS: Harmine exhibited potent effects on both autophagy and apoptosis. Treatment with harmine could enhance dots of GFP-LC3 in cells. Meanwhile, the process had connection with Beclin-1, LC3-II, and p62 by the inhibition of Akt/mTOR/p70S6K signaling. However, high concentration of harmine led to apoptosis characterized by the propidium/Annexin V-positive cell pollution, cell shrunk and the collapse of mitochondrial membrane potential. The regulation of Bcl-2, Bax and the gathering of cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 contributed to the induction of apoptosis. In addition, 10μM LY294002 (a specific inhibitor of PI3K/Akt) combination with 40μM harmine significantly increased the cytotoxicity to the gastric cancer cells and up-regulated both the apoptosis-related protein (cleaved-PARP, cleaved-caspase-3) and autophagy-related protein (Beclin-1, LC3-II, and p62). Adding the inhibitor of autophagy, 3-MA or BafA1, increased the viability of harmine-exposured gastric cancer cells, which confirmed the role of autophagy played in the gastric cancer cell death induced by harmine | ||
| 520 | |a CONCLUSION: Harmine might be a potent inducer of apoptosis and autophagy, which offered evidences to therapy of harmine in gastric carcinoma in the folk medicine | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a Gastric cancer | |
| 650 | 4 | |a Harmine | |
| 650 | 4 | |a mTOR | |
| 650 | 7 | |a Antineoplastic Agents, Phytogenic |2 NLM | |
| 650 | 7 | |a Apoptosis Regulatory Proteins |2 NLM | |
| 650 | 7 | |a BECN1 protein, human |2 NLM | |
| 650 | 7 | |a Beclin-1 |2 NLM | |
| 650 | 7 | |a Harmine |2 NLM | |
| 650 | 7 | |a 4FHH5G48T7 |2 NLM | |
| 650 | 7 | |a Phosphatidylinositol 3-Kinases |2 NLM | |
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| 650 | 7 | |a EC 3.4.22.- |2 NLM | |
| 650 | 7 | |a Caspase 9 |2 NLM | |
| 650 | 7 | |a EC 3.4.22.- |2 NLM | |
| 700 | 1 | |a Wang, Yihai |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chunhua |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Xiaomin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Mingya |e verfasserin |4 aut | |
| 700 | 1 | |a He, Xiangjiu |e verfasserin |4 aut | |
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