Mechanism of melittin for anti-tumor effects: Research status and future perspectives
- 1 Wuhan No.2 High School, Wuhan City, Hubei Province, China, 430015
* Author to whom correspondence should be addressed.
Abstract
Cancer is a primary cause of mortality in humans. Conventional chemotherapy has hazardous side effects and numerous limitations, necessitating the urgent exploration of novel anti-cancer agents. Based on existing literature and data, this article reviews the anti-tumor mechanism, current application status, and future development of bee venom peptides. The research findings demonstrate that bee venom peptide, a natural cell lytic peptide, possesses many anti-tumor mechanisms, including the direct destruction of tumor cells, the induction of tumor cell apoptosis, and immunological modulation. It can disrupt the integrity of the cell membrane and lead to cell death. It can also activate apoptosis signaling pathways through endoplasmic reticulum, mitochondria, and death receptors, promoting apoptosis of tumor cells. Meanwhile, it can reshape the immune microenvironment and stimulate immune responses. The author also discussed issues such as poor stability, low bioavailability, lack of targeting, and potential safety of bee venom peptides. In the future, it is recommended to develop new derivatives of bee venom peptides and optimize combination therapy strategies.
Keywords
melittin, tumor, immunoregulation, combination therapy strategy
[1]. Kiri, S., & Ryba, T. (2024). Cancer, metastasis, and the epigenome. Molecular Cancer, 23(1).
[2]. Nasir, A., Khan, A., Li, J., et al. (2021). Nanotechnology, a tool for diagnostics and treatment of cancer. Current Topics in Medicinal Chemistry, 21(15), 1360-1376.
[3]. Yu, X., Jia, S., Yu, S., et al. (2023). Recent advances in melittin-based nanoparticles for antitumor treatment: from mechanisms to targeted delivery strategies. Journal of Nanobiotechnology, 21(1).
[4]. Laurindo, L. F., de Lima, E. P., Laurindo, L. F., et al. (2024). The therapeutic potential of bee venom-derived Apamin and Melittin conjugates in cancer treatment: A systematic review. Pharmacological Research, 209.
[5]. Guha, S., Ferrie, R. P., Ghimire, J., et al. (2021). Applications and evolution of melittin, the quintessential membrane active peptide. Biochemical Pharmacology, 193.
[6]. Liu, C.-c., Hao, D.-j., Zhang, Q., et al. (2016). Application of bee venom and its main constituent melittin for cancer treatment. Cancer Chemotherapy and Pharmacology, 78(6), 1113-1130.
[7]. Cheng, B., Thapa, B., K. C. R., et al. (2015). Dual secured nano-melittin for the safe and effective eradication of cancer cells. Journal of Materials Chemistry B, 3(1), 25-29.
[8]. Liu, J., Xiao, S., Li, J., et al. (2018). Molecular details on the intermediate states of melittin action on a cell membrane. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1860(11), 2234-2241.
[9]. Tsujimoto, Y. (1998). Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria? Genes Cells, 3(11), 697-707.
[10]. Ucker, D. S., & Levine, J. S. (2018). Exploitation of apoptotic regulation in cancer. Frontiers in Immunology, 9.
[11]. Sangboonruang, S., Kitidee, K., Chantawannakul, P., et al. (2020). Melittin from Apis florea venom as a promising therapeutic agent for skin cancer treatment. Antibiotics, 9(8).
[12]. Luo, Y., Xu, C.-m., Luo, B., et al. (2023). Melittin treatment prevents colorectal cancer from progressing in mice through ER stress-mediated apoptosis. Journal of Pharmacy and Pharmacology, 75(5), 645-654.
[13]. Zhang, B. L., Lu, S.-q., Li, Y., Su, Y.-h., & Ling, C.-q. (2007). Effects of melittin on expressions of mitochondria membrane protein 7A6, cell apoptosis-related gene products Fas and Fas ligand in hepatocarcinoma cells. Journal of Chinese Integrative Medicine, 5(5), 559-563.
[14]. Li, X., Zhu, S., Li, Z., et al. (2022). Melittin induces ferroptosis and ER stress-CHOP-mediated apoptosis in A549 cells. Free Radical Research, 56(5-6), 398-410.
[15]. Gasanoff, E., Liu, Y., Li, F., et al. (2021). Bee venom melittin disintegrates the respiration of mitochondria in healthy cells and lymphoblasts, and induces the formation of non-bilayer structures in model inner mitochondrial membranes. International Journal of Molecular Sciences, 22(20).
[16]. Sun, Y., Yang, Y.-M., Hu, Y.-Y., et al. (2022). Inhibition of nuclear deacetylase Sirtuin-1 induces mitochondrial acetylation and calcium overload leading to cell death. Redox Biology, 53.
[17]. Li, X., Li, Z., Meng, Y.-Q., et al. (2023). Melittin kills A549 cells by targeting mitochondria and blocking mitophagy flux. Redox Report, 28(1).
[18]. Green, D. R. (2022). The death receptor pathway of apoptosis. The Death Receptor Pathway of Apoptosis, 14(2).
[19]. Jo, M., Park, M. H., Kollipara, P. S., et al. (2012). Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicology and Applied Pharmacology, 258(1), 72-81.
[20]. Yu, X., Dai, Y., Zhao, Y., et al. (2020). Melittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response. Nature Communications, 11(1).
[21]. Hou, G., Li, Y., Wang, Q., et al. (2022). iRGD-grafted N-trimethyl chitosan-coated protein nanotubes enhanced the anticancer efficacy of curcumin and melittin. International Journal of Biological Macromolecules, 222, 348-359.
Cite this article
Li,Y. (2025). Mechanism of melittin for anti-tumor effects: Research status and future perspectives. Journal of Clinical Technology and Theory,2,33-37.
Data availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
Disclaimer/Publisher's Note
The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of EWA Publishing and/or the editor(s). EWA Publishing and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
About volume
Journal：Journal of Clinical Technology and Theory
© 2024 by the author(s). Licensee EWA Publishing, Oxford, UK. This article is an open access article distributed under the terms and
conditions of the Creative Commons Attribution (CC BY) license. Authors who
publish this series agree to the following terms:
1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons
Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this
series.
2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published
version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial
publication in this series.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and
during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See
Open access policy for details).