Table 1.
Studies of melittin effects in cancer cells.
| Cancer type |
Model/organism(s) | Form of melittin | Effect | Ref. |
|---|---|---|---|---|
| Lung | A549 and NCI-H460 cells | Bee venom (BV) containing 45-50% melittin | Inhibited cell growth, induced apoptotic cell death | 103 |
| Breast | MCa cells and transplanted tumor in CBA mice | Purified BV, intravenous (IV) and subcutaneous (SC) | IV injection reduced metastatic nodes in the lung | 104 |
| Ovary | A2780cp cells | BV + cisplatin | Apoptotic cell killing, greater in combination than individual treatment | 105 |
| Prostate | LNCaP, DU145, PC-3 cells and BALB/c athymic nude mice | Intraperitoneal (IP) BV, melittin peptide | Inhibition of cell growth, inhibition of tumor growth and apoptotic cell death | 106 |
| Prostate | PC-3 cells | Polyethylenimine-chlorotoxin nanoparticles containing melittin DNA | Decreased cell viability | 107 |
| Ovary | SKOV-3 and PA-1 cells | BV, melittin peptide | Induction of apoptotic cell death | 108 |
| Ovary | SKOV-3 cells | Urokinase-type plasminogen activator amino acids 1-43 conjugated to melittin | Inhibit cell growth, arrest cell cycle, induce apoptosis | 109 |
| Liver | HepG2 cells | Melittin peptide | Inhibition of cell growth | 110 |
| Ovary | A2780 cells | Melittin peptide | Reduced metabolic pathways in synergism with cisplatin | 111 |
| Bone | MG63 cells | Melittin peptide | Induction of apoptotic cell death | 112 |
| Bone | BALB/c nu/nu mice and UMR-106 cells and endothelial progenitor cells (EPCs) | Intratumor multi-point local injections of melittin peptide | Decreased EPC functions, reduced tumor size | 113 |
| Stomach | AGS cells | Melittin peptide | Inhibited proliferation and induced cell death | 114 |
| Stomach | SGC-7901 cells | Melittin peptide | Induction of apoptosis | 115 |
| Stomach | NUGC-3, MKN-7, and MKN-74 cells | Monomeric and dimeric melittin peptide | Monomeric peptide more cytotoxic at low concentrations, cell membrane disruption, nuclear localization | 116 |
| Liver | BEL-7402 cells | Adenovirus containing the α-fetoprotein gene and the melittin gene (Ad-rAFP-Mel) | Inhibition of cell proliferation, induction of apoptosis, upregulation of Fas expression | 117 |
| Liver | MHCC97L and MHCC97H cells, Transplanted liver tumor in nude mice | Tail vein injection of melittin peptide | Inhibits cancer cell viability and motility, suppresses Rac1 activity | 118 |
| Liver | Hep3B, HepG2, SMMC-7721 and BEL-7402 cells | Melittin peptide in combination with TNF-related apoptosis-inducing ligand (TRAIL) | Induction of apoptosis in synergism with TRAIL | 119 |
| Liver | SMMC-7721 cells | Melittin peptide | Inhibits cell proliferation, delays cell cycle progression | 120 |
| Liver | MHCC97-H, Bel-7402, L02, HepG2, SMMC7721, Hep3B and Huh7 cells | Melittin peptide | Inhibition of cellular proliferation, invasion and angiogenesis | 121 |
| Liver | HepG-2, MHCC97-H and AsPC-1 cells, BALB/c and BALB/c athymic nude mice | IV injection of VEGF165-melittin fusion protein | Inhibition of cells highly expressing VEGFR-2 and inhibition of tumor xenograft growth | 122 |
| Liver | SMCC-7221 and HepG2 cells | Hydrocarbon stapled variants of melittin | Increased stability in α-helix and against proteolytic degradation, enhanced anti-cancer cell activity of melittin | 123 |
| Bone marrow | L1210, L5178Y and HL-60 cells | Melittin peptide | Inhibition of cell growth and clonogenicity | 124 |
| Bone marrow | U937 cells | Melittin peptide | Membrane disruption, cell hypertrophy, aggregation and cytolysis | 125 |
| Bone marrow | U937 cells overexpressing Bcl-2 | Melittin peptide | Induction of apoptosis through regulation of Akt signaling pathway | 126 |
| Bone marrow | CCRF-CEM and K-562 cells | Melittin peptide | Reduced cell viability, induced apoptosis | 127 |
| Breast | MDA-MB-231 and MCF-7 cells | Melittin peptide | Inhibition of cellular invasion and migration | 128 |
| Brain | U87 cells | Nanoparticles composed of pristine graphene, nanographene oxide, graphite, nanodiamond and hierarchical nanoporous carbons containing melittin peptide | Increased cell death relative to melittin alone | 129 |
| Breast | 4T1 cells | Melittin peptide | Greater cytotoxicity and hemolysis than cisplatin and doxorubicin, induced apoptosis, upregulation of Drp1 and Mfn1 mRNA | 130 |
| Breast | MCF-7 and MDA-MB-231 cells | Estrone conjugated polyion complex micelle containing melittin peptide | Micelles increased cytotoxicity and cellular uptake of melittin into cells | 131 |
| Kidney | Caki-1 cells | Melittin peptide | Inhibition of invasion and migration, suppression of MMP-9 expression | 132 |
| Cervix | CaSki cells | Melittin peptide | Suppression of EGF-induced migration and angiogenesis, inhibited expression of HIF-1α | 133 |
| Cervix | HeLa cells | Melittin peptide | Induction of apoptosis | 134 |
| Cervix | HeLa cells | Graphene oxide based magnetic nanocomposites containing melittin peptide | Pore formation in membranes and cell lysis, less degradation and continuous release of melittin | 135 |
| Esophagus | ECA109 and TE13 cells, subcutaneous injection into BALB/c nude mice | IP melittin peptide, radiation | Enhanced sensitization to radiation followed by increased apoptosis, delayed growth of tumor | 136 |
| Bladder | T24 and 5637 cells | Melittin peptide | Suppression of cell proliferation and migration | 137 |
| Bladder | UM-UC-3 and 5637 cells | Melittin peptide | Inhibition of proliferation, migration and invasion | 138 |
| Colorectal | HCT-116 and SW-480 cells | Melittin peptide | Reduced cell viability, induction of apoptosis and necrosis, increased expression of Fas receptors and caspase 9 and mRNA involved in apoptosis and biotransformation | 139 |
| Colorectal and gastric | AGS, COLO205 and HCT-15 cells | Melittin peptide | Induction of cell death, changes in membrane morphology and membrane damage | 140 |
| Prostate | Sprague-Dawley rats with complete Freund’s adjuvant induced prostatitis | Melittin peptide | Raised the pain threshold, decreased inflammation and demonstrated analgesic effects | 141 |
| Lung | Highly metastatic mouse Lewis lung carcinoma cells (hm LLC) in vitro and SC injection into C57BL/6 mice, VEGF transfected HUVEC cells | Melittin peptide | Inhibits tumor growth and angiogenesis in mice, decreases VEGFR inflammation and targets VEGFR and COX-2 signaling pathway | 142 |
| Lung | LLC cells SC injected into C57BL/6 cells and in vitro LLC, MLE12, A549, and H441 cells | Rhodamine conjugated melittin peptide | Reduced tumor growth and angiogenesis, increased survival, decreased macrophage in tumor environment, preferentially bound M2 macrophages, increased M1/M2 ratio | 143 |
| Lung | ChaGo-K1 and THP-1 cells | Melittin peptide | Induction of apoptosis and G1 cell cycle arrest, inhibition of differentiation into TAMs, reduced colony formation | 144 |
| Lung | A549 cells SC injected into BALB/C nude mice | Melittin peptide | Inhibited invasion and migration, suppressed tumor growth, decreased expression of VEGF and HIF-1α | 145 |
| Lung | NCI-H441, A549 and BEAS-2B cells and NCI-H441 cells SC injected into BALB/C nu/nu mice | Melittin peptide | Inhibition of cell growth, migration, invasion and miR-183 expression, inhibition of tumor growth, induction of apoptosis | 146 |
| Lung, liver and ovary | CTLL-2 cells and SMMC-7721, A549 and SKOV3 cells were SC injected into BALB/c mice | Mutant IL-2 fused to melittin peptide | Induced proliferation of lymphocytes, promoted production of IFN-γ, inhibited cancer cell proliferation, inhibited tumor growth, prevented metastases | 147 |
| Lung | RAW264.7 cells and LLC cells SC injected into C57BL/6 cells | Melittin fused to dKLA peptide | Induction of M2 macrophage death, membrane disruption leading to apoptosis, reduction of tumor growth and angiogenesis, targeting of M2-like TAMs | 148 |
| Skin | A2058 cells | Melittin peptide and BV | Melittin contributes in large part to BV induced apoptosis and elevation of calcium | 149 |
| Skin and breast | MCF7 and A375 cells | Melittin peptide | Synergistic effect of melittin targeting with plasma induced oxidation | 150 |
| Pancreas | SW1990, Capan1, AsPC-1 and BxPC-3 cells, SW1990 cells SC injected into nude mice | Melittin peptide | Inhibited cell growth, induced apoptosis and cell cycle arrest, downregulated biosynthetic pathways, induced gemcitabine sensitization in vitro and in vivo | 151 |
| Thyroid | TT cells, TT cells injected intradermally into nude mice | Melittin derivative, TT1 peptide | Suppressed tumor growth, induced cell death and apoptosis, upregulated Bax, downregulated Bcl-2, activated caspases 3 and 9 | 152 |
| Brain | C6 rat astrocytoma cells | Melittin peptide | Inhibition of calmodulin and cell growth | 153 |
| Brain | Rat C6 glioma cells in vitro and injected SC into BALB/c nude mice | (RADA)8-GG-melittin hydrogel | Reduced tumor size and tumor recurrence rate | 154 |
| Brain | U87 and bEnd.3 cells, intracranial U87 xenogrsfts in ICR and BALB/c nude mice | Lipodisk loaded with paclitaxel and melittin | Paclitaxel and melittin showed synergism in vitro, loaded disks prolonged survival time in mice | 155 |
| Breast | NHA and 231BR cells, intracardiac injections of 231BR cells into NCr nu/nu mice | Nanoparticles with surface AMD3100, containing a modified promelittin gene | Increased accumulation of melittin in tumor cells, inhibited tumor progression, enhanced survival of tumor bearing mice | 156 |
| Head and neck | CNE-2 and KB cells, SC injection of CNE-2 cells into BALB/C nude mice | Melittin peptide | Inhibition of cell growth, induction of apoptosis, reduction in HIF-1α and VEGF expression, reduction in tumor growth | 157 |