Cytotoxic and Antimicrobial Activities of Aporphine Alkaloids Isolated fromStephania venosa(Blume) Spreng

Makarasen, Arthit; Sirithana, Wandee; Mogkhuntod, Samang; Khunnawutmanotham, Nisachon; Chimnoi, Nitirat; Techasakul, Supanna

doi:10.1055/s-0030-1270743

Cited by 43 publications

(40 citation statements)

References 25 publications

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“…Crebanine exhibits a variety of biological properties including, anti-microbial activities, improvement of neurodegenerative diseases, as well as antiinvasion and anti-proliferation activities in cancer cells. [14][15][16] Moreover, our previous report demonstrated that crebanine reduced TNF-α induced lung cancer cells proliferation and invasion via suppressing NF-κB activity.…”

Section: 13)mentioning

confidence: 96%

Antiinflammatory Activities of Crebanine by Inhibition of NF-κB and AP-1 Activation through Suppressing MAPKs and Akt Signaling in LPS-Induced RAW264.7 Macrophages

Intayoung

Limtrakul

Yodkeeree

2016

Biological & Pharmaceutical Bulletin

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Crebanine, an aporphine alkaloid, displays various biological activities such as anticancer and antimicrobial activities. In this study, we further investigated the suppressive effect of crebanine on lipopolysaccharide (LPS)-induced expression of proinflammatory mediators and the molecular mechanisms underlying these activities in RAW264.7 macrophages. Crebanine inhibited the production of proinflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha in LPS-induced RAW264.7 cells. Moreover, crebanine suppressed LPS-induced inducible nitric oxide (iNO) and prostaglandin E 2 and reduced the expression of iNO synthase and cyclooxygenase-2 in RAW264.7 cells. Crebanine suppressed LPS-induced phosphorylation of Akt and mitogen-activated protein kinases (MAPKs), including extracellular signalingregulated kinase 1/2, c-Jun NH 2 -terminal kinase, and p38 MAPK signaling. In addition, the specific inhibitor of MAPKs and Akt reduced the expression of IL-6 and NO production in LPS-induced macrophages. Furthermore, crebanine inhibited LPS-induced nuclear factor kappa B (NF-κB) activation by reducing the phosphorylation of p65 at Ser536 but not the p65 translocation to the nucleus and inhibitory factor kappa B alpha degradation. Crebanine also suppressed phosphorylation and nucleus translocation of activator protein-1 (AP-1). These observations suggest that the antiinflammatory properties of crebanine may stem from the inhibition of proinflammatory mediators via suppression of the NF-κB, AP-1, MAPKs, and Akt signaling pathways.

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Section: 13)mentioning

confidence: 96%

Antiinflammatory Activities of Crebanine by Inhibition of NF-κB and AP-1 Activation through Suppressing MAPKs and Akt Signaling in LPS-Induced RAW264.7 Macrophages

Intayoung

Limtrakul

Yodkeeree

2016

Biological & Pharmaceutical Bulletin

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“…20,21) Previous studies have shown that crebanine displayed cytotoxic and anti-cancer activities in many cancer cells, including A549 lung carcinoma cells, MCF-7 breast cancer cells, MOLT-3 lymphoblastic leukemic cells, and HL-60 cells. 13) However, the underlying mechanisms of this compound on growth inhibition are not well understood. The present study found that crebanine exerted significant growth inhibition effects on solid tumor and leukemic cells but had a slight effect on normal fibroblast cells.…”

Section: Discussionmentioning

confidence: 99%

“…The structure of crebanine was elucidated by extensive spectroscopic analysis (UV, IR, MS, 1 H-NMR, 13 C-NMR) and the molecular formula was identified as crebanine, C 20 H 21 NO 4 .…”

Section: Methodsmentioning

confidence: 99%

“…12) Alkaloids are the main bioactive components of this genus and some of them such as aporphine, bisbenzylisoquinoline, cepharanthine, dehydrocrebanine, and crebanine exhibited anti-proliferative activity in cancer cells. 13,14) According to our previous report, crebanine (chemical structure shown in Fig. 1) was isolated from the tuber of S. venosa and has shown potent cytotoxicity in various cancer cell lines, e.g., leukemic cell, gastric carcinoma cells and hepatoma cells.…”

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Induction of G1 Arrest and Apoptosis in Human Cancer Cells by Crebanine, an Alkaloid from Stephania venosa

et al. 2012

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In this study, we focused the effects of crebanine, an alkaloid isolated from the tuber of Stephania venosa, on various human cancer cells. Crebanine treatment was found to significantly inhibit the proliferation of human leukemic cells (HL-60, U937 and K562), human fibrosarcoma cells (HT1080) and cervix cancer cell lines (KB-3-1 and KB-V1), of which HL-60 cells were the most sensitive to its treatment. In contrast, crebanine caused much less toxicity in human normal fibroblast cells. Our results demonstrated that crebanine mediated cell cycle arrest at G0/G1 phase and this was associated with down-regulation of cyclins A and D. In addition, crebanine induced apoptosis, which was detected by observation of the membrane phospholipid exposure in flow cytometry. Its induction of apoptosis was accompanied by an increase in cleavage of caspase-3, -8, -9 and poly(ADP-ribose) polymerase (PARP), and was attributable to the augmentation of Bax/Bcl proteins level. Crebanine also decreased mitochondrial membrane potential. Taken together, crebanine exerts anti-proliferative effects on human cancer cells through the induction of cell cycle arrest at the G1 phases and apoptosis. Our results suggest that crebanine is a promising new candidate as a chemotherapeutic agent for cancer therapy.

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“…14,15) Tubers of Stephania venosa (BLUME) SPRENG (S. venosa) have been used in traditional medicine in nerve tonics, aphrodisiacs, appetizers, and to treat asthma, microbial infection, hyperglycemia, malaria and cancer. 16,17) This genus is also well known as a rich source of alkaloids which exhibit a variety of pharmacological activities including being an antioxidant, as well as being antiarrhythymic, and contributing to the antiproliferation of cancer. 18,19) From our previous study, we demonstrated that crebanine from S. venosa induced cancer cell apoptosis and cell cycle arrest.…”

mentioning

confidence: 99%

Anti-invasion Effect of Crebanine and O-Methylbulbocapnine from Stephania venosa via Down-Regulated Matrix Metalloproteinases and Urokinase Plasminogen Activator

et al. 2013

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The alkaloids isolated from Stephania venosa (S. venosa) have been shown to inhibit the proliferation and to induce the apoptosis of cancer cells. However, the anti-metastatic effect of the alkaloids on cancer cell invasion is unknown. In this study, we investigated the anti-invasive properties of four alkaloids from S. venosa, crebanine (CN), O-methylbulbocapnine (OMBC), tetrahydropalmatine (THP), and N-methyltetrahydropalmatine (NMTHP), in HT1080 human fibrosacroma cells. Treatment of the cells with 15 µg/mL of CN and OMBC reduced the chemo-invasion of HT1080 cells to 45 and 50%, respectively, whereas THP and NMTHP had a negative effect. On the other hand, CN and OMBC had no effect on cell migration. Matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) are the extracellular matrix (ECM) degradation enzymes that play an important role in cancer cell metastasis. Results from zymography and western blot analysis showed that CN and OMBC comparatively reduced MMP-2, MMP-9, MT1-MMP and uPA expression in a dose-dependent manner. However, CN and OMBC had no effect on the activity of collagenase, MMP-2 and MMP-9. We also found that CN and OMBC reduced the nuclear translocation and DNA binding activity of nuclear factor kappa B (NF-κB), which is the expressed mediator of ECM degradation enzymes. These findings demonstrated that CN and OMBC mediated HT1080 cell invasion by the reduction of MMP-2, MMP-9, uPA and MT1-MMP expression, possibly by targeting of NF-κB signaling pathway in the HT1080 cells.

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Cytotoxic and Antimicrobial Activities of Aporphine Alkaloids Isolated fromStephania venosa(Blume) Spreng

Cited by 43 publications

References 25 publications

Antiinflammatory Activities of Crebanine by Inhibition of NF-κB and AP-1 Activation through Suppressing MAPKs and Akt Signaling in LPS-Induced RAW264.7 Macrophages

Antiinflammatory Activities of Crebanine by Inhibition of NF-κB and AP-1 Activation through Suppressing MAPKs and Akt Signaling in LPS-Induced RAW264.7 Macrophages

Induction of G1 Arrest and Apoptosis in Human Cancer Cells by Crebanine, an Alkaloid from <i>Stephania venosa</i>

Anti-invasion Effect of Crebanine and <i>O</i>-Methylbulbocapnine from <i>Stephania venosa</i> <i>via</i> Down-Regulated Matrix Metalloproteinases and Urokinase Plasminogen Activator

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