Bee Venom and Its Peptide Component Melittin Suppress Growth and Migration of Melanoma Cells via Inhibition of PI3K/AKT/mTOR and MAPK Pathways

Lim, Haet Nim; Baek, Seung Bae; Jung, Hye Jin

doi:10.3390/molecules24050929

Cited by 67 publications

(50 citation statements)

References 37 publications

(49 reference statements)

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“…Besides, melittin can induce apoptosis in gastric cancer cells through the mitochondria pathways and its concomitant increased generation of free radicals [25]. Melittin can also induce caspase-dependent apoptosis in melanoma cells also by displaying a downregulation of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), mammalian Target of Rapamycin (mTOR) and 5' adenosine monophosphate-activated protein kinase (MAPK) signaling pathways [21]. Moreover, melittin can also affect the growth of human hepatoma cells via HDAC2-mediated PTEN upregulation, AKT inactivation and inhibition of the previous mentioned PI3K/AKT signaling pathway [73].…”

Section: Melittinmentioning

confidence: 99%

Bee Venom: An Updating Review of Its Bioactive Molecules and Its Health Applications

2020

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Bee venom (BV) is usually associated with pain since, when humans are stung by bees, local inflammation and even an allergic reaction can be produced. BV has been traditionally used in ancient medicine and in acupuncture. It consists of a mixture of substances, principally of proteins and peptides, including enzymes as well as other types of molecules in a very low concentration. Melittin and phospholipase A2 (PLA2) are the most abundant and studied compounds of BV. Literature of the main biological activities exerted by BV shows that most studies focuses on the comprehension and test of anti-inflammatory effects and its mechanisms of action. Other properties such as antioxidant, antimicrobial, neuroprotective or antitumor effects have also been assessed, both in vitro and in vivo. Moreover, human trials are necessary to confirm those clinical applications. However, notwithstanding the therapeutic potential of BV, there are certain problems regarding its safety and the possible appearance of adverse effects. On this perspective, new approaches have been developed to avoid these complications. This manuscript is aimed at reviewing the actual knowledge on BV components and its associated biological activities as well as the latest advances on this subject.

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Section: Melittinmentioning

confidence: 99%

Bee Venom: An Updating Review of Its Bioactive Molecules and Its Health Applications

2020

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“…Melittin is in routine use as a non-steroidal anti-inflammatory reagent for the relief of pain and the treatment of chronic inflammatory diseases (13,14). Moreover, melittin has demonstrated the ability to inhibit cancer cell proliferation and induce apoptosis (15,16). Compared with other pro-apoptotic proteins such as p53, Bak and Bax, melittin is not selective, damaging both healthy and cancer cells.…”

Section: Introductionmentioning

confidence: 99%

TERT promoter regulating melittin expression induces apoptosis and G<sub>0</sub>/G<sub>1</sub> cell cycle arrest in esophageal carcinoma cells

Zhou

et al. 2020

Oncol Lett

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Esophageal squamous cell carcinoma accounts for a large proportion of cancer-associated mortalities in both men and women. Melittin is the major active component of bee venom, which has been reported to possess anti-inflammatory, antibacterial and anti-cancer properties. The aim of the present study was to construct a tumor targeted recombinant plasmid [pc-telomerase reverse transcriptase (TERT)-melittin] containing a human TERT promoter followed by a melittin coding sequence and to explore the effects of this plasmid in esophageal cell carcinoma and investigate preliminarily the underlying mechanisms of this effect. TE1 cells were transfected with pcTERT-melittin and the resulting apoptosis was subsequently examined. The viability of TE1 cells transfected with pcTERT-melittin was measured using a Cell Counting Kit-8 assay, which indicated inhibited proliferation. The disruption of mitochondrial membranes and the concomitant production of reactive oxygen species demonstrated an inducible apoptotic effect of melittin in TE1 cells. Apoptotic cells were also counted using an Annexin V-FITC and PI double-staining assay. The upregulation of cleaved caspase-9, cleaved caspase-3, Bax and poly(ADP-ribose) polymerase 1 in pcTERT-melittin transfected TE1 cells, suggested that pcTERT-melittin-induced apoptosis was associated with the mitochondrial pathway. TE1 cells were also arrested in the G 0 /G 1 phase when transfected with pcTERT-melittin, followed by the decline of CDK4, CDK6 and cyclin D1 expression levels. As cell invasion and metastasis are common in patients with esophageal cancer, a cell migration assay was conducted and it was found that pcTERT-melittin transfection reduced the migratory and invasive abilities of TE1 cells. The findings of the present study demonstrated that pcTERT-melittin may induce apoptosis of esophageal carcinoma cells and inhibit tumor metastasis.

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“…Some studies have demonstrated that the PI3K/AKT/mTOR signaling pathway could regulate the growth and metastasis of melanoma cells [21,22]. However, whether miR-33a-5p could regulate the PI3K/AKT/mTOR signaling pathway in melanoma has not been investigated.…”

mentioning

confidence: 99%

miR-33a-5p inhibits the growth and metastasis of melanoma cells by targeting SNAI2

Zhang¹,

Yang²

2020

neo

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MicroRNAs have been verified as critical regulators in the development of melanoma. MiR-33a-5p was significantly downregulated in melanoma. However, the specific role and regulatory mechanism of miR-33a-5p in melanoma were still unclear. The present study identified that miR-33a-5p was downregulated in melanoma tissues and cells, while SNAI2 was upregulated. MiR-33a-5p directly targeted SNAI2 and negatively regulated its expression in melanoma cells. Overexpression of miR-33a-5p repressed proliferation, migration, invasion, EMT and promoted apoptosis of melanoma cell in vitro, these effects were partially reversed by SNAI2 overexpression. In addition, miR-33a-5p impaired melanoma growth in vivo by inhibiting SNAI2. Mechanistically, miR-33a-5p repressed activation of the PI3K/AKT/mTOR pathway by targeting SNAI2. In conclusion, miR-33a-5p repressed the progression of melanoma by targeting SNAI2 via inactivation of the PI3K/AKT/mTOR signaling pathway, providing a potential molecular mechanism for the treatment of melanoma.

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Bee Venom and Its Peptide Component Melittin Suppress Growth and Migration of Melanoma Cells via Inhibition of PI3K/AKT/mTOR and MAPK Pathways

Cited by 67 publications

References 37 publications

Bee Venom: An Updating Review of Its Bioactive Molecules and Its Health Applications

Bee Venom: An Updating Review of Its Bioactive Molecules and Its Health Applications

TERT promoter regulating melittin expression induces apoptosis and G<sub>0</sub>/G<sub>1</sub> cell cycle arrest in esophageal carcinoma cells

miR-33a-5p inhibits the growth and metastasis of melanoma cells by targeting SNAI2

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