Desacetyl nimbinene inhibits breast cancer growth and metastasis through reactive oxygen species mediated mechanisms

Arumugam, Arunkumar; Subramani, Ramadevi; Nandy, Sushmita; Powell, Sara; Velazquez, Marissa; Orozco, Alexis; Galvez, Adriana; Lakshmanaswamy, Rajkumar

doi:10.1007/s13277-015-4468-x

Cited by 13 publications

(7 citation statements)

References 40 publications

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“…Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) is an important signaling pathway that is involved in tumor cell growth, proliferation, apoptosis, metabolism, angiogenesis, metastasis and immunity [8–10]. It also has a close connection with the NF-κB signaling pathway, in which the phosphorylation of Akt can activate NF-κB [11], triggering the regulation of downstream MMP-2 and MMP-9, regulating cancer cell proliferation, migration and invasion [12, 13].…”

Section: Introductionmentioning

confidence: 99%

MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS

et al. 2019

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BackgroundBreast cancer is one of the most commonly diagnosed cancers in women, with high morbidity and mortality. Tumor metastasis is implicated in most breast cancer deaths; thus, inhibiting metastasis may provide a therapeutic direction for breast cancer. In the present study, pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) was used to inhibit metastasis in MCF-7 breast cancer cells.MethodsUptake of MPPa was detected by fluorescence microscopy. Cell viability was evaluated by the Cell Counting Kit-8 (CCK-8). ROS generation was detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). The migration of cells was assessed by wound healing assay, and invasion ability was assessed by Matrigel invasion assay. Levels of MMP2 and MMP9 were measured by PCR. Akt, phospho-Akt (Ser473), phospho-NF-κB p65 (Ser536) and NF-κB p65 were measured by western blotting. The F-actin cytoskeleton was observed by immunofluorescence. Lung tissue was visualized by hematoxylin and eosin staining.ResultsFollowing MPPa-PDT, migration and invasion were decreased in the MCF-7 cells. MPPa-PDT downregulated the expression of MMP2 and MMP9, which are responsible for the initiation of metastasis. MPPa-PDT reduced the phosphorylation of Akt and NF-κB. MPPa-PDT also reduced the expression of F-actin in cytoskeleton in MCF-7 cells. These effects were blocked by the reactive oxygen species scavenger NAC or the Akt activator SC79, while the PI3K inhibitor LY294002 or the Akt inhibitor triciribine enhanced these effects. Moreover, MPPa-PDT inhibited tumor metastasis and destroyed F-actin in vivo.ConclusionTaken together, these results demonstrate that MPPa-PDT inhibits the metastasis of MCF-7 cells both in vitro and in vivo and may be involved in the Akt/NF-κB-dependent MMP-9 signaling pathway. Thus, MPPa-PDT may be a promising treatment to inhibit metastasis.

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Section: Introductionmentioning

confidence: 99%

MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS

et al. 2019

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“…Previous studies deciphering the anti-metastatic effects of phytochemicals have shown sodium danshensu significantly inhibits the migration and invasion of human oral cancer cells by downregulating the phosphorylation of p38 [ 21 ]. Similarly, other bioactive plant compounds, such as Kahweol acetate and desacetylnimbinene, have been shown to inhibit cancer metastasis by reducing the phosphorylation of p38 [ 22 , 23 ]. All these observations are in line with our findings, which justify the significant involvement of p38 signaling pathway in mediating anti-metastatic effects of platyphyllenone [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

PlatyphyllenoneExerts Anti-Metastatic Effects on Human Oral Cancer Cells by Modulating Cathepsin L Expression, MAPK Pathway and Epithelial–Mesenchymal Transition

Velmurugan

Lin

Mahalakshmi³

et al. 2021

IJMS

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Advanced-stage oral cancers with lymph node metastasis are associated with poor prognosis and a high mortality rate. Although recent advancement in cancer treatment has effectively improved the oral cancer prognosis, the majority of therapeutic interventions are highly expensive and are associated with severe sideeffects. In the present study, we studied the efficacy of a diarylheptanoid derivative, platyphyllenone, in modulating the metastatic potential of human oral cancer cells. Specifically, we treated the human oral cancer cells (FaDu, Ca9-22, and HSC3) with different concentrations of platyphyllenone and measured the cell proliferation, migration, and invasion. The study findings revealed that platyphyllenonesignificantly inhibited the motility, migration, and invasion of human oral cancer cells. Mechanistically, platyphyllenone reduced p38 phosphorylation, decreased β-catenin and Slug, increased E-cadherin expression, and reduced cathepsin L expression, which collectively led to a reduction in cancer cell migration and invasion. Taken together, our study indicates that platyphyllenone exerts significant anti-metastatic effects on oral cancer cells by modulating cathepsin L expression, the MAPK signaling pathway, and the epithelial–mesenchymal transition process.

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“…Several studies have shown that extract of neem leaves has bioactivity which can inhibit the growth of cancer cells [1]. Desacetylnimbin is one of the compounds in the extract of neem leaves which can prevent the growth of breast cancer cells through apoptosis mechanism [2]. Azadirachtin has potential as an inhibitory compound for the growth of cervical cancer cells [3].…”

Section: Introductionmentioning

confidence: 99%

Potential Use of Compounds from Neem Leaves (Azadirachta indica Juss) as PPARg and ERa Inhibitors to Control Breast Cancer Cell Growth In Silico Model

Supriyanto

Rifa’i

Yunianta

et al. 2020

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Treatment using herbs is currently growing rapidly. Compounds in herbal plants can cure various degenerative diseases. The study aims to analyze the potency of nimbin, deacetylnimbin, salanin, and deacetylsalanin compounds in the neem leaves extract to inhibit target proteins namely PPARg and ERa. PPARg is the main regulator of the function of adipose tissue microvascular endothelial cells (aMVECs) while ERa is a protein that mediates all estrogen effects and it is important in the growth of prostate and breast cancer. Inhibition of ERa can prevent the proliferation and growth of breast cancer cells by affecting the performance of estrogen which binds to hormonal receptors and causes inhibition of breast cancer cell proliferation. The results of in silico analysis show that deacetylnimbin can inhibit ERa protein. The docking analysis shows that deacetylnimbin has the potential to replace tamoxifen as a breast cancer drug. The other studies such in vitro and in vivo are needed to validate in silico study.

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Desacetyl nimbinene inhibits breast cancer growth and metastasis through reactive oxygen species mediated mechanisms

Cited by 13 publications

References 40 publications

MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS

MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS

PlatyphyllenoneExerts Anti-Metastatic Effects on Human Oral Cancer Cells by Modulating Cathepsin L Expression, MAPK Pathway and Epithelial–Mesenchymal Transition

Potential Use of Compounds from Neem Leaves (Azadirachta indica Juss) as PPARg and ERa Inhibitors to Control Breast Cancer Cell Growth In Silico Model

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