Propionibacterium acnes Augments Antitumor, Anti-Angiogenesis and Immunomodulatory Effects of Melatonin on Breast Cancer Implanted in Mice.
Breast cancer is one of the most invasive cancers with high mortality. The immune stimulating Propionibacterium acnes is a Gram positive bacterium that has the ability to cause inflammation and activate Th1-type cytokine immune response. Antitumor response was associated with the inflammation induced by P. acnes, but the antitumor effect of this bacterium was not evaluated in combination with other agents. The aim of this study was to test the antitumor potential of a combination of melatonin and P. acnes against breast cancer implanted in mice. Balb/C mice were transplanted with EMT6/P cell line and in vivo antitumor effect was assessed for P. acnes, melatonin, and a combination of melatonin and P. acnes. Tumor and organs sections were examined using hematoxylin/eosin staining protocol, and TUNEL colorimetric assay was used to detect apoptosis. The expression of vascular endothelial growth factor (VEGF) was measured in tumor sections and serum levels of INF-γ, and IL-4 were measured to evaluate the immune system function. To evaluate the toxicity of our combination, AST and ALT levels were measured in the serum of treated mice. The combination of melatonin and P. acnes has high efficiency in targeting breast cancer in mice. Forty percent of treated mice were completely cured using this combination and the combination inhibited metastasis of cancer cells to other organs. The combination therapy reduced angiogenesis, exhibited no toxicity, induced apoptosis, and stimulates strong Th1-type cytokine antitumor immune response. The combination of melatonin and P. acnes represents a promising option to treat breast cancer. However, carful preclinical and clinical evaluation is needed before considering this combination for human therapy.
Department of Clinical Pharmacy and Therapeutics, Applied Science University, Amman, Jordan.
Wamidh H
WH
Talib
Department of Pharmaceutical Sciences and Pharmaceutics, Applied Science University, Amman, Jordan.
Suhair
S
Saleh
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003124:Colorimetry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation / Q000473:pathology*; D011425:Propionibacterium acnes / Q000187:drug effects / Q000502:physiology*; D013194:Staining and Labeling; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007155:Immunologic Factors; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4; D007371:Interferon-gamma; D008550:Melatonin