ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2020; 11(20):6038-6049. doi:10.7150/jca.48296 This issue Cite
Research Paper
Surfactin from Bacillus subtilis attenuates ambient air particulate matter-promoted human oral cancer cells metastatic potential
1. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
2. Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County 61363, Taiwan.
3. Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Puzi City, Chiayi County 61363, Taiwan.
4. Department of Safety Health and Environmental Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan.
5. College of Medicine, Chang Gung University, Guishan Dist., Taoyuan City 33303, Taiwan.
6. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
7. Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan.
8. Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
9. Department of Respiratory Care, Chang Gung University of Science and Technology, Puzi City, Chiayi County 613, Taiwan.
10. Division of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County 613, Taiwan.
11. Department of Pediatrics, Division of Pediatric Hematology/Oncology and Neonatology, Yunlin Chang Gung Memorial Hospital, Yunlin, Taiwan.
12. College of Medicine, Chang Gung University, Taoyuan, Taiwan.
#These authors contributed equally to this work.
Abstract
Recently, many studies have indicated that ambient air particulate matter (PM) can increase the risk of oral cancer. The most common malignant tumor in the oral cavity is oral squamous cell carcinoma (OSCC). Usually, cancer cell migration/invasion is the most important cause of cancer mortality. Matrix metalloproteinase-2 (MMP-2) and MMP-9 have been shown to play important roles in regulating metastasis and the tumor microenvironment. Here, we studied the anti-cancer effects of surfactin, a cyclic lipopeptide generated by Bacillus subtilis, on cancer cell migration and invasion. Surfactin suppressed PM-promoted cell migration and invasion and colony formation of SCC4 and SCC25 human oral squamous cell carcinoma cell lines. We observed that PM induced MMP-2 and MMP-9 expression, which was inhibited by surfactin. Transfection with p65, p50, c-Jun, c-Fos, p85, p110, Akt, mammalian target of rapamycin (mTOR), or interleukin-6 (IL-6) siRNA markedly inhibited PM-induced MMP-2 and MMP-9 expression. Moreover, surfactin could reduce Akt, mTOR, p65, and c-Jun activation and IL-6 secretion induced by PM. Finally, we proved that transfection with Akt, p65, or c-Jun siRNA significantly inhibited PM-induced IL-6 release. Taken together, these results suggest that surfactin functions as a suppressor of PM-induced MMP2/9-dependent oral cancer cell migration and invasion by inhibiting the activation of phosphoinositide 3-kinase (PI3K)/Akt/mTOR and PI3K/Akt/nuclear factor-κB (NF-κB) and activator protein-1 (AP-1)/IL-6 signaling pathways.
Keywords: Surfactin, Invasion, Particulate matter, Oral cancer, Matrix metalloproteinase
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