| Autor: |
Bandi DR; Department of Applied Microbiology, Sri Padmavathi Mahila Viswavidyalayam, Tirupati 517502, Andhra Pradesh, India., Chitturi CMK; Department of Applied Microbiology, Sri Padmavathi Mahila Viswavidyalayam, Tirupati 517502, Andhra Pradesh, India., Aswathanarayan JB; Department of Microbiology, JSS Academy of Higher Education & Research (JSS AHER), Mysore 570015, Karnataka, India., Veeresh PKM; Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysore 570015, Karnataka, India., Bovilla VR; Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysore 570015, Karnataka, India., Sukocheva OA; Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia., Devi PS; Department of Applied Microbiology, Sri Padmavathi Mahila Viswavidyalayam, Tirupati 517502, Andhra Pradesh, India., Natraj SM; Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysore 570015, Karnataka, India., Madhunapantula SV; Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysore 570015, Karnataka, India.; Special Interest Group (SIG) in Cancer Biology and Cancer Stem Cells (CBCSC), JSS Academy of Higher Education & Research (JSS AHER), Mysore 570015, Karnataka, India. |
| Abstrakt: |
Breast cancer (BC) continues to be one of the major causes of cancer deaths in women. Progress has been made in targeting hormone and growth factor receptor-positive BCs with clinical efficacy and success. However, little progress has been made to develop a clinically viable treatment for the triple-negative BC cases (TNBCs). The current study aims to identify potent agents that can target TNBCs. Extracts from microbial sources have been reported to contain pharmacological agents that can selectively inhibit cancer cell growth. We have screened and identified pigmented microbial extracts (PMBs) that can inhibit BC cell proliferation by targeting legumain (LGMN). LGMN is an oncogenic protein expressed not only in malignant cells but also in tumor microenvironment cells, including tumor-associated macrophages. An LGMN inhibition assay was performed, and microbial extracts were evaluated for in vitro anticancer activity in BC cell lines, angiogenesis assay with chick chorioallantoic membrane (CAM), and tumor xenograft models in Swiss albino mice. We have identified that PMB from the Exiguobacterium (PMB1), inhibits BC growth more potently than PMB2, from the Bacillus subtilis strain. The analysis of PMB1 by GC-MS showed the presence of a variety of fatty acids and fatty-acid derivatives, small molecule phenolics, and aldehydes. PMB1 inhibited the activity of oncogenic legumain in BC cells and induced cell cycle arrest and apoptosis. PMB1 reduced the angiogenesis and inhibited BC cell migration. In mice, intraperitoneal administration of PMB1 retarded the growth of xenografted Ehrlich ascites mammary tumors and mitigated the proliferation of tumor cells in the peritoneal cavity in vivo. In summary, our findings demonstrate the high antitumor potential of PMB1. |
