Bee venom inhibits tumor angiogenesis and metastasis by inhibiting tyrosine phosphorylation of VEGFR-2 in LLC-tumor-bearing mice

Huh, Jungwon; Baek, Yong-Hyeon; Lee, Minho; Choi, Dong‐Hee; Park, Dong-Suk; Lee, Jae-Dong

doi:10.1016/j.canlet.2009.11.013

Cited by 75 publications

(51 citation statements)

References 37 publications

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“…VEGF has been shown to be an important cytokine that induces a series of biological effects in ECs (25,26). our previous study proved that blocking VEGF-A in EC9706 supernatant inhibited the endothelial-like differentiation of iDCs (8), which is consistent with the report that in mouse ovarian carcinomas, Su5416, a VEGF receptor tyrosine kinase inhibitor, abolished the vascular migration of CD11c + cells, confirming the importance of tyrosine kinase signaling in DC endothelialization (1).…”

Section: Discussionsupporting

confidence: 86%

VEGF-A not Ang2 mediates endothelial-like differentiation of immature DCs by ERK1/2 signaling in the microenvironment of human colon adenocarcinoma

Lü

Liu²,

Zhao³

et al. 2011

Int J Oncol

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Abstract. Endothelial-like differentiation of dendritic cells (DCs) is an interesting and significant phenomenon, which is worth further investigation. Here, we show that the tumor microenvironment derived from the supernatant of the SW620 human colon adenocarcinoma cell line and colon adenocarcinoma tissue homogenate can promote immature DCs (iDCs) to differentiate from the DC pathway toward endothelial cells, while the peri-carcinoma homogenate supernatant does not have this role. Inhibition of angiopoietin-2 (Ang2) in the supernatant by its antibody has no obvious influence on the endotheliallike differentiation. In contrast, inhibition of vascular endothelial growth factor-A (VEGF-A) blocked the differentiation. During the course of differentiation, a sustained activation of ERK1/2 was detected. PD98059 blocked the phosphorylation of ERK1/2 as well as the endothelial-like differentiation of iDCs. Inhibition of VEGF-A also blocked the phosphorylation of ERK1/2. These data suggest that VEGF-A not Ang2 mediates endothelial-like differentiation of iDCs by ERK1/2 signaling in the microenvironment of human colon adenocarcinoma.

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Section: Discussionsupporting

confidence: 86%

VEGF-A not Ang2 mediates endothelial-like differentiation of immature DCs by ERK1/2 signaling in the microenvironment of human colon adenocarcinoma

Lü

Liu²,

Zhao³

et al. 2011

Int J Oncol

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“…The possible molecular targets of BV and its components for inhibition of cancer cell growth are numerous and different [28]. Previous studies have shown that BV and its components induce apoptosis via activation of caspase [7,8,29,30], phospholipases A2 (PLA2) [31], matrix metalloproteinase-2 (MMP-2) [32] and VEGF [28,33]. In this study, we demonstrated that BV inhibited cancer cell growth in NSCLC (non-small cell lung cancer) A549 and NCI-H460 cells through the induction of apoptosis via increase of DR expression and inhibition of NF-κB pathway.…”

Section: Discussionmentioning

confidence: 99%

Cancer Cell Growth Inhibitory Effect of Bee Venom via Increase of Death Receptor 3 Expression and Inactivation of NF-kappa B in NSCLC Cells

Choi

Hwang

et al. 2014

Toxins

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Our previous findings have demonstrated that bee venom (BV) has anti-cancer activity in several cancer cells. However, the effects of BV on lung cancer cell growth have not been reported. Cell viability was determined with trypan blue uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related protein expression was determined with Western blotting. An EMSA was used for nuclear factor kappaB (NF-κB) activity assay. BV (1–5 μg/mL) inhibited growth of lung cancer cells by induction of apoptosis in a dose dependent manner in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell death, expression of DR3 and DR6 was significantly increased. However, deletion of DRs by small interfering RNA significantly reversed BV induced cell growth inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax) was concomitantly increased, but the NF-κB activity and expression of Bcl-2 were inhibited. A combination treatment of tumor necrosis factor (TNF)-like weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer cell growth with further down regulation of NF-κB activity. These results show that BV induces apoptotic cell death in lung cancer cells through the enhancement of DR3 expression and inhibition of NF-κB pathway.

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“…Also, Jo et al found that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of JAK2/STAT3 pathway (Jo et al, 2012). Authors also concluded that BV takes effect by blocking the tyrosine phosphorylation of VEGFR-2 so as exerting anti-angiogenic activity, and validate the application of BV in lung cancer treatment (Huh et al, 2010). A recent study by Liu et al found that melittin derived from the venom of the bee inhibits cell motility drastically and prevents HCC metastasis via inhibition of Rac1 (Liu et al, 2008).…”

Section: Antitumor Activity Of Bee Venommentioning

confidence: 90%

“…It contains at least 18 kinds of active compounds, including melittin (a major component of BV), apamin, adolapin, the mast-cell-degranulating (MCD) peptide, enzymes (phospholipase A2, and hyaluronidase) as well as non-peptide components, such as histamine, dopamine, and norepinephrine which have a variety of pharmaceutical properties . Recent studies reported several effects of bee venom such as induction of apoptosis and necrosis and effects on proliferation, cytotoxicity, and growth inhibition of different types of cancer cells, including prostate cancer (Park et al, 2011), breast cancer (Ip et al, 2008), ovarian cancer (Jo et al, 2012), lung cancer (Huh et al, 2010), liver cancer (Liu et al, 2008), bladder cancer (Ip et al, 2012) as well as leukemia (Moon et al, 2006). BV induces apoptotic cell death through several cancer cell death mechanisms, among them the activation of PLA2 by melittin is the critical mechanism for the anti-cancer activity of BV.…”

Section: Antitumor Activity Of Bee Venommentioning

confidence: 99%

Biotoxins for Cancer Therapy

Liu

Yang²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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In recent times, a number of studies have provided evidence that biotoxins present great potential as antitumor agents, such as snake venom, bee venom, some bacteria toxins and plant toxins, and thus could be used as chemotherapeutic agents against tumors. The biodiversity of venoms and toxins make them a unique source from which novel anticancer agent may be developed. Biotoxins, also known as natural toxins, include toxic substances produced by plants, animals and microorganisms. Here, we systematically list representative biological toxins that have antitumor properties, involving animal toxins, plant toxins, mycotoxins as well as bacterial toxins. In this review, we summarize the current knowledge involving biotoxins and the active compounds that have anti-cancer activity to induce cytotoxic, antitumor, immunomodulatory, and apoptotic effects in different tumor cells in vivo or in vitro. We also show insights into the molecular and functional evolution of biotoxins.

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Bee venom inhibits tumor angiogenesis and metastasis by inhibiting tyrosine phosphorylation of VEGFR-2 in LLC-tumor-bearing mice

Cited by 75 publications

References 37 publications

VEGF-A not Ang2 mediates endothelial-like differentiation of immature DCs by ERK1/2 signaling in the microenvironment of human colon adenocarcinoma

VEGF-A not Ang2 mediates endothelial-like differentiation of immature DCs by ERK1/2 signaling in the microenvironment of human colon adenocarcinoma

Cancer Cell Growth Inhibitory Effect of Bee Venom via Increase of Death Receptor 3 Expression and Inactivation of NF-kappa B in NSCLC Cells

Biotoxins for Cancer Therapy

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