Anti-tumor and anti-metastasis activities of honey bee larvae powder by suppressing the expression of EZH2

• Published in: Biomedicine & pharmacotherapy 2018-09, Vol.105, p.690-696
• Main Authors: Kageyama, Masakatsu, Li, Kejuan, Sun, Shuang, Xing, Guoqing, Gao, Ran, Lei, Zhongfang, Zhang, Zhenya
• Format: Article
• Language: English
• Subjects: Animals; Anti-metastasis; Anti-tumor; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Bees - chemistry; Cell Line, Tumor; Cell Survival - drug effects; Enhancer of Zeste Homolog 2 Protein - antagonists & inhibitors; Enhancer of Zeste Homolog 2 Protein - biosynthesis; EZH2 level; Female; Honey bee larvae; Humans; Larva - chemistry; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; MCF-7 Cells; Melanoma, Experimental - drug therapy; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Mice; Mice, Inbred BALB C; Powders
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.06.034

[Display omitted] •Oral administration of HLP significantly suppressed tumor growth and lung metastasis in BALB/c xenograft mice.•HLP was safe for mice and HLE did not induce any toxic effect in vitro.•HLE contained 34 amino acids, which accounted for 42.37% of the total extract.•HLE significantly decreased the level of EZH2 mRNA in tumor cells. Honey bee larvae products have been widely used as traditional daily supplements and complementary medicine for health promotion. However, there is little scientific evidence about their bioactivities. This study was designed to examine the anti-tumor and anti-metastasis effects of honey bee larvae powder (HLP) and explore the underlying mechanism. A subcutaneous transplantation model (murine breast cancer cell 4T1-LUC) and lung metastasis model (murine melanoma cell B16-F10) were established to evaluate the anti-tumor and anti-metastasis effects of HLP. Honey bee larvae powder extract (HLE) was obtained by 70% ethanol extraction, and its chemical composition was determined according to physiochemical methods. Cell Counting Kit-8 assay was performed to test the cytotoxicity of HLE, and qRT-PCR assays were conducted to examine the mRNA levels of tumor marker EZH2 in HLE-treated tumor cells. In vivo xenograft tumor assays in BALB/c mice revealed dose-dependent suppression of tumor growth and lung metastasis showing an inhibition rate of 37.5% and 70.4% at 6 g/kg HLP-administered group with no toxicity to the animals. In vitro studies indicated that HLE showed no cytotoxicity to cancer cells at doses up to 1000 μg/mL, however, it significantly decreased EZH2 mRNA levels in HLE (1000 μg/mL)-treated B10-F10 cells (28.49%) and 4T1-LUC cells (26.75%). Further studies to elucidate the mechanisms involved and to isolate the active components of honey bee larva may provide more valuable information for its development and application in cancer treatment.