melitten and Bone-Neoplasms

Apitherapy (using bee products) has gained broad recognition in cancer therapeutics globally. Honeybee venom has a broad range of biological potential, and its utilization is rapidly emerging in apitherapy. Bee products have significant potential to strengthen the immune system and improve human health. Thus, this review is targeted toward recapitulating the chemo-preventive potential of melittin (MEL), which constitutes a substantial portion of honeybee venom. Honeybee venom (apitoxin) is produced in the venom gland of the honeybee abdomen, and adult bees utilize it as a primary colony defense mechanism. Apitoxin comprises numerous biologically active compounds, including peptides, enzymes, amines, amino acids, phospholipids, minerals, carbohydrates, and volatile components. We are mainly focused on exploring the potential of melittin (a peptide component) of bee venom that has shown promising potential in the treatment of several human cancers, including breast, stomach, lung, prostate, ovary, kidney, colon, gastric, esophageal, cervical cancers, melanoma, osteosarcoma, and hepatocellular carcinoma. This review has summarized all potential studies related to the anticancerous efficacy of melittin (apitoxin), its formulations, conjugates, and nano-formulations against several human carcinomas, which would further pave the way for future researchers in developing potent drugs for cancer management.

Topics: Animals; Bee Venoms; Bees; Bone Neoplasms; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Male; Melitten; Peptides

Osteosarcoma is the most commonly seen type of primary malignant bone tumors in children and adolescents. Partial patients with osteosarcoma cannot tolerate the side effects of chemotherapy drugs. Hence, it is urgent to find anti-osteosarcoma drugs with low side effects. Melittin is an anti-tumor Traditional Chinese Medicine with low side effects. The purpose of this study was to explore the anti-osteosarcoma effect of melittin and its possible molecular mechanisms.. The effects of melittin on cell growth were detected by CCK-8, clonal formation, and flow cytometry. The related molecules were also investigated by Real-time PCR and Western blot. A xenograft model in nude mice was established to observe the effects of melittin on tumor growth and the related molecular expression was detected by immunohistochemistry.. Melittin can inhibit the proliferation of osteosarcoma 143B cells, reduce colony formation, and induce apoptosis while significantly up-regulating the expression of Bax and Caspase-3 and down-regulating the expression of Bcl-2 proteins. Moreover, treatment with melittin significantly reduced the mRNA and protein levels of β-catenin and Wnt/β- catenin related genes (LRP5, c-Myc, and Survivin) in osteosarcoma 143B cells in vitro. The xenograft model found that melittin significantly inhibited tumor growth and decreased the protein expression levels of β-catenin and Wnt/β- catenin related genes in vivo.. These findings show that melittin could inhibit the growth of osteosarcoma 143B cells, which may be related to the inhibition of Wnt/β-catenin signaling pathway activity and induce apoptosis by up-regulating the ratio of Bax/Bcl-2 in osteosarcoma 143B cells. Therefore, melittin is a promising anti-tumor drug for the treatment of osteosarcoma.

Topics: Adolescent; Animals; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; beta Catenin; Bone Neoplasms; Caspase 3; Cell Line, Tumor; Cell Proliferation; Child; Humans; Melitten; Mice; Mice, Nude; Osteosarcoma; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Sincalide; Survivin; Wnt Signaling Pathway

Melittin is a major active peptide component of bee venom that has been demonstrated to show anti-tumor effects. Osteosarcoma is a type of bone tumor with a high degree of malignancy, and metastasis is the main challenge of osteosarcoma therapy. This study aimed to investigate the role of melittin in the lung metastasis of osteosarcoma. 143 B cells were treated with different concentrations of melittin in vitro. Wound-healing and transwell assays were performed to determine the cell migration and invasion potential. Quantitative real-time PCR and Western blot experiments were performed to evaluate the expression levels of Wnt/β-catenin signaling pathway-related factors after treatment with melittin. The orthotopic implantation model and hematoxylin-eosin staining were used to investigate the effect of melittin treatment on tumor formation and lung metastasis. Immunohistochemical staining and Western blot experiments were performed to indicate the melittin-mediated expression changes in Wnt/β-catenin signaling pathway-related factors. The cell migration and invasion potential were observed to be inhibited in a dose-dependent manner upon treatment with melittin. Treatment with medium and high concentrations of melittin attenuated the mRNA and protein expression of LRP5, β-catenin, MMP-2, cyclin D, c-Myc, survivin, MMP-9, and VEGF genes in vitro. Melittin significantly inhibited the growth of tibia xenografts in nude mice and decreased the number of lung metastatic nodules. Consistent with the results observed in vitro, treatment with melittin at medium and high concentrations attenuated the expression of Wnt/β-catenin signaling pathway-related factors in vivo. In vitro, Wnt/β-catenin signaling pathway was involved in Melittin-mediated -migration and invasion potential of 143 B cells. Similarly, as observed in the in vivo experiments, Wnt/β-catenin signaling pathway was also associated with the role of melittin on lung metastasis of osteosarcomas.

Topics: Animals; Bone Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Humans; Lung Neoplasms; Melitten; Mice; Mice, Nude; Osteosarcoma; Wnt Signaling Pathway

Endothelial progenitor cells (EPCs) are important in tumor angiogenesis. Stromal cell-derived factor-1α (SDF-1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4) are key in stem cell homing. Melittin, a component of bee venom, exerts antitumor activity, however, the underlying mechanisms remain to be elucidated. The present study aimed to assess the effects of melittin on EPCs and angiogenesis in a mouse model of osteosarcoma. UMR‑106 cells and EPCs were treated with various concentrations of melittin and cell viability was determined using the MTT assay. EPC adherence, migration and tube forming ability were assessed. Furthermore, SDF‑1α, AKT and extracellular signal‑regulated kinase (ERK)1/2 expression levels were detected by western blotting. Nude mice were inoculated with UMR‑106 cells to establish an osteosarcoma mouse model. The tumors were injected with melittin, and its effects were assessed by immunohistochemistry and immunofluorescence. Melittin decreased the viability of UMR‑106 cells and EPCs. In addition, it decreased EPC adhesion, migration and tube formation when compared with control and SDF‑1α‑treated cells. Melittin decreased the expression of phosphorylated (p)‑AKT, p‑ERK1/2, SDF‑1α and CXCR4 in UMR‑106 cells and EPCs when compared with the control. The proportions of cluster of differentiation (CD)34/CD133 double‑positive cells were 16.4±10.4% in the control, and 7.0±4.4, 2.9±1.2 and 1.3±0.3% in tumors treated with 160, 320 and 640 µg/kg melittin per day, respectively (P<0.05). At 11 days, melittin reduced the tumor size when compared with that of the control (control, 4.8±1.3 cm3; melittin, 3.2±0.6, 2.6±0.5, and 2.0±0.2 cm3 for 160, 320 and 640 µg/kg, respectively; all P<0.05). Melittin decreased the microvessel density, and SDF‑1α and CXCR4 protein expression levels in the tumors. Melittin may decrease the effect of osteosarcoma on EPC‑mediated angiogenesis, possibly via inhibition of the SDF-1α/CXCR4 signaling pathway.

Topics: Animals; Biomarkers; Bone Neoplasms; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Survival; Chemokine CXCL12; Disease Models, Animal; Endothelial Progenitor Cells; Extracellular Signal-Regulated MAP Kinases; Humans; Male; Melitten; Mice; Neovascularization, Pathologic; Osteosarcoma; Proto-Oncogene Proteins c-akt; Receptors, CXCR4; Signal Transduction; Tumor Burden; Xenograft Model Antitumor Assays