Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma

Ling, Chang Quan; Li, B.; Zhang, C.; Zhu, Desheng; Huang, Xin; Gu, Wanyi; Li, S.-X.

doi:10.1093/annonc/mdi019

Cited by 50 publications

(27 citation statements)

References 30 publications

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“…In a previous study, we have shown that an MMP2 cleavable melittin, the poreforming toxin from honey bee, conjugated with avidin can specifically target tumor cells in vitro and in vivo (20). It has also been shown that recombinant adenovirus encoding a melittin gene controlled by an AFP promoter is effective against hepatocellular carcinoma in vivo (21). In the present study, an MMP2 cleavable fusion gene between LAP and melittin was constructed.…”

Section: Introductionmentioning

confidence: 78%

In vitro- and in vivo-targeted tumor lysis by an MMP2 cleavable melittin-LAP fusion protein

Holle

Song²,

Holle³

et al. 2009

Int J Oncol

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Abstract. Chemotherapy is one of the main treatment options for cancer, but the effectiveness of chemotherapeutic drugs is severely limited due to their systemic toxicity. Therefore, the need for a more targeted approach in tumor treatment is obvious. A tumor-activated agent would decrease systemic toxicity as well as increase the efficacy of the treatment. It has previously been shown that the latency of pro-TGF-ß is conferred by dimerization of two latency-associated peptides (LAP) that form a protective shield, which is cleaved off upon activation by matrix metalloproteinases (MMPs). It has also been shown that the fusion of this LAP peptide with other cytokines can confer their latency. In the present study, a recombinant adenovirus with a fusion gene encoding a tumor-activated pro-cytolytic peptide was made in which the LAP domain of TGF-ß was fused with melittin, a potent cytolytic toxin, with an MMP2 cleavage site in between the two. In vitro studies show that the melittin-MMP2-LAP recombinant adenovirus can be activated by MMP2 which leads to the release of free melittin to lyse the target cells. In vivo studies show approximately a 70% decrease in B16 tumor volume in melittin-MMP2-LAP recombinant adenovirustreated mice as compared to control mice. No significant systemic toxicity was observed in the treated mice.

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Section: Introductionmentioning

confidence: 78%

In vitro- and in vivo-targeted tumor lysis by an MMP2 cleavable melittin-LAP fusion protein

Holle

Song²,

Holle³

et al. 2009

Int J Oncol

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“…To avoid this adverse effect and attempt to achieve a specific killing action on liver cancer, the recombinant adenovirus Ad-rAFP-Mel was constructed with the Mel gene, the α-fetoprotein (AFP) gene and replication-defective adenovirus. Prior results showed that Ad-rAFP-Mel could specifically inhibit proliferation of AFP-producing human hepatocarcinoma cells in vitro and in vivo [6]. The aim of the present study is to observe the effect of Ad-rAFP-Mel on inducing cell apoptosis and interfering with the cell cycle.…”

Section: Introductionmentioning

confidence: 91%

Growth Arrest and Apoptosis of the Human Hepatocellular Carcinoma Cell Line Bel-7402 Induced by Melittin

Bai

Gu²,

Zhang³

et al. 2006

Oncol Res Treat

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Objective: The aim of this study was to investigate the cellular effects of melittin on the growth and apoptosis of human hepatocellular carcinoma (HCC) cells and to provide the molecular mechanism for potential application of a recombinant adenovirus carrying the melittin gene (Ad-rAFP-Mel) in the treatment of liver cancer. Methods: Human HCC cells (BEL-7402) were infected with Ad-rAFPMel at different times. In vitro cell growth was determined by MTT assay. Cellular apoptosis was evaluated quantitatively and qualitatively by phase-contrast microscopy, transmission electron microscopy, DNA ladder electrophoresis, TUNEL staining and flow cytometry. Results: Ad-rAFP-Mel infection had an inhibitory effect on the proliferation of BEL-7402 cells. The morphological changes of apoptosis were confirmed by microscopy and DNA electrophoresis. The ultrastructural characteristics of apoptotic cells, such as chromatin condensation and nuclear fragmentation, were also observed by electron microscopy in the Ad-rAFP-Mel-infected cells. Ad-rAFPMel infection markedly induced cellular apoptosis, and Fas expression on Bel-7402 cells infected by Ad-rAFPMel was up-regulated. Conclusion: The fact that melittin can induce apoptosis of the HCC cell line BEL-7402 leads us to consider adenovirus-mediated delivery of melittin as a promising approach for the treatment of HCC. However, the underlying mechanism needs to be further investigated.

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“…The efficiency of adenovirus-mediated gene transferred to BEL-7402 cells was 100% when the multiplicity of infection of Ad-rAFP-Mel was 10 in vitro , and was also high in vivo . The inhibitive rates of recombinant adenovirus Ad-rAFP-MEL for SMMC7721 cells, BEL7402 cells and L-02 cells were about 16.1%, 66.2% and 7.5%, respectively, similarly, the inhibitive rates for recombinant adenovirus Ad-CMV-MEL for the same cells were about 65.9%, 58.9% and 31.7%, respectively whereas a significant antineoplastic effect was observed in vivo by intratumoral injection of Ad-rAFP-MEL [78, 79]. …”

Section: Anticancer Effects Of Bv and Its-conjugatesmentioning

confidence: 99%

Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy

et al. 2017

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Melittin (MEL), a major peptide component of bee venom, is an attractive candidate for cancer therapy. This agent has shown a variety of anti-cancer effects in preclinical cell culture and animal model systems. Despite a convincing efficacy data against variety of cancers, its applicability to humans has met with challenges due to several issues including its non-specific cytotoxicity, degradation and hemolytic activity. Several optimization approaches including utilization of nanoparticle based delivery of MEL have been utilized to circumvent the issues. Here, we summarize the current understanding of the anticancer effects of bee venom and MEL on different kinds of cancers. Further, we also present the available information for the possible mechanism of action of bee venom and/or MEL.

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Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma

Abstract: Ad-rAFP-Mel can inhibit specifically proliferation of AFP-producing human hepatocarcinoma cells in vitro and in vivo. This suggests that animal toxin gene can be used as an antitumor gene.

Cited by 50 publications

References 30 publications

In vitro- and in vivo-targeted tumor lysis by an MMP2 cleavable melittin-LAP fusion protein

In vitro- and in vivo-targeted tumor lysis by an MMP2 cleavable melittin-LAP fusion protein

Growth Arrest and Apoptosis of the Human Hepatocellular Carcinoma Cell Line Bel-7402 Induced by Melittin

Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy

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