Phospholipase A2-independent Ca2+ entry and subsequent apoptosis induced by melittin in human MG63 osteosarcoma cells

Chu, Sau-Tung; Cheng, He‐Hsiung; Huang, Chun-Ta; Chang, Hong-Chiang; Chi, Chao-Chuan; Su, Hsing‐Hao; Hsu, Shu-Shong; Wang, Jue‐Long; Chen, I-Shu; Liu, Shiuh–Inn; Lu, Yih-Chau; Huang, Jong‐Khing; Ho, Chin-Man; Jan, Chung‐Ren

doi:10.1016/j.lfs.2006.09.024

Cited by 62 publications

(32 citation statements)

References 32 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from the caspase-dependent pathway, these authors also suggested a caspase-independent pathway through expression of apoptosis-inducing factor (AIF) and endonuclease G (Endo G) in the Ca Ski cells. A similar mechanism of bee venom was confi rmed in human breast cancer MCF7 cells (49), U937 cells (50), and in human MG63 osteosarcoma cells (47). Data by Wang et al (51) suggest that melittin can synergize with TRAIL in the induction of human hepatocellular carcinoma cell (HCC) apoptosis, and that the combination of melittin with tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) may be a promising therapeutic approach in the treatment of TRAIL-resistant human cancer.…”

Section: Figure 4 Effect Of Bee Venom On Recovery From Bleomycin-indumentioning

confidence: 53%

“…The authors found that honeybee venom induced calcium-dependent but caspase-independent apoptotic cell death in human melanoma A2058 cells, but not in normal skin fi broblast Detroit 551 cells. They suggested that treatment of A2058 cells with melittin, the key component of bee venom, resulted in similar elevation of calcium levels and cell death (47). Observations by Ip et al (48) indicated that bee venom induced cell cycle arrest and apoptosis in human cervical epidermoid carcinoma Ca Ski cells via a Fas receptor pathway, involving mitochondrial-dependent pathways, and that it is closely related to the level of cytoplasmic Ca 2+ in Ca Ski cells.…”

Section: Figure 4 Effect Of Bee Venom On Recovery From Bleomycin-indumentioning

confidence: 97%

See 1 more Smart Citation

Potentiation of Bleomycin Lethality in HeLa and V79 Cells by Bee Venom

Oršolić

2009

Archives of Industrial Hygiene and Toxicology

View full text Add to dashboard Cite

This study investigated possible growth-inhibiting effects of bee venom applied alone or in combination with a cytotoxic drug bleomycin on HeLa and V79 cells in vitro based on clone formation, cell counting, and apoptosis. Melittin, the key component of bee venom, is a potent inhibitor of calmodulin activity, and also a potent inhibitor cell growth and clonogenicity. Intracellular accumulation of melittin correlates with the cytotoxicity of antitumour agents. Previous studies indicated that some calcium antagonists and calmodulin inhibitors enhanced intracellular levels of antitumor agents by inhibiting their outward transport. In this study, treatment of exponentially growing HeLa and V79 cells with bleomycin caused a dose-dependent decrease in cell survival due to DNA damage. This lethal effect was potentiated by adding a non-lethal dose of the bee venom. By preventing repair of damaged DNA, bee venom inhibited recovery from potentially lethal damage induced by bleomycin in V79 and HeLa cells. Apoptosis, necrosis, and lysis were presumed as possible mechanisms by which bee venom inhibited growth and clonogenicity of V79 cells. HeLa cells, on the other hand, showed greater resistance to bee venom. Our fi ndings suggest that bee venom might fi nd a therapeutic use in enhancing cytotoxicity of antitumour agent bleomycin.

show abstract

Section: Figure 4 Effect Of Bee Venom On Recovery From Bleomycin-indumentioning

confidence: 53%

Section: Figure 4 Effect Of Bee Venom On Recovery From Bleomycin-indumentioning

confidence: 97%

Potentiation of Bleomycin Lethality in HeLa and V79 Cells by Bee Venom

Oršolić

2009

Archives of Industrial Hygiene and Toxicology

View full text Add to dashboard Cite

show abstract

“…It increased IC in osteoblast-like cells [32], fibroblasts [33], hepatocytes [16,34] and mast cells [35]. In human osteoblasts, melittin increased IC levels only when calcium was present extracellularly and not from intracellular stores [32].…”

Section: Discussionmentioning

confidence: 98%

High content analysis to determine cytotoxicity of the antimicrobial peptide, melittin and selected structural analogs

et al. 2011

View full text Add to dashboard Cite

Antimicrobial peptides (AMPs) are naturally occurring entities with potential as pharmaceutical candidates and/or food additives. They are present in many organisms including bacteria, insects, fish and mammals. While their antimicrobial activity is equipotent with many commercial antibiotics, current limitations are poor pharmacokinetics, stability and potential toxicology issues. Most elicit antimicrobial action via perturbation of bacterial membranes. Consequently, associated cytotoxicity in human cells is reflected by their capacity to lyse erythrocytes. However, more rigorous toxicological assessment of AMPs is required in order to predict potential failure at a later stage of development. We describe a high-content analysis (HCA) screening protocol recently established for determination and prediction of safety in pharmaceutical drug discovery. HCA is a powerful, multi-parameter bioanalytical tool that amalgamates the actions of fluorescence microscopy with automated cell analysis software in order to understand multiple changes in cellular health. We describe the application of HCA in assessing cytotoxicity of the cytolytic α-helical peptide, melittin, and selected structural analogues. The data shows that structural modification of melittin reduces its cytotoxic action and that HCA is suitable for rapidly identifying cytotoxicity.

show abstract

“…We demonstrate that the contact-mediated transfer of melittin by nanoparticles produces cytochrome c release and apoptosis. Previously, cellular apoptosis from melittin exposure of cells has been attributed to calcium entry or activation of phospholipase A2 (66,67). The details of the nanoparticle mechanism of melittin delivery remain to be revealed, but the exclusive apoptotic cell destruction suggests that the cell-surface membrane remains intact and that intracellular membranes are being disrupted.…”

Section: Discussionmentioning

confidence: 99%

Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth

Soman¹,

Baldwin²,

Hu³

et al. 2009

J. Clin. Invest.

258

278

View full text Add to dashboard Cite

The in vivo application of cytolytic peptides for cancer therapeutics is hampered by toxicity, nonspecificity, and degradation. We previously developed a specific strategy to synthesize a nanoscale delivery vehicle for cytolytic peptides by incorporating the nonspecific amphipathic cytolytic peptide melittin into the outer lipid monolayer of a perfluorocarbon nanoparticle. Here, we have demonstrated that the favorable pharmacokinetics of this nanocarrier allows accumulation of melittin in murine tumors in vivo and a dramatic reduction in tumor growth without any apparent signs of toxicity. Furthermore, direct assays demonstrated that molecularly targeted nanocarriers selectively delivered melittin to multiple tumor targets, including endothelial and cancer cells, through a hemifusion mechanism. In cells, this hemifusion and transfer process did not disrupt the surface membrane but did trigger apoptosis and in animals caused regression of precancerous dysplastic lesions. Collectively, these data suggest that the ability to restrain the wide-spectrum lytic potential of a potent cytolytic peptide in a nanovehicle, combined with the flexibility of passive or active molecular targeting, represents an innovative molecular design for chemotherapy with broad-spectrum cytolytic peptides for the treatment of cancer at multiple stages.

show abstract

Phospholipase A2-independent Ca2+ entry and subsequent apoptosis induced by melittin in human MG63 osteosarcoma cells

Cited by 62 publications

References 32 publications

Potentiation of Bleomycin Lethality in HeLa and V79 Cells by Bee Venom

Potentiation of Bleomycin Lethality in HeLa and V79 Cells by Bee Venom

High content analysis to determine cytotoxicity of the antimicrobial peptide, melittin and selected structural analogs

Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth

Contact Info

Product

Resources

About