title: Anti-tumor activity of staurosporine in the tumor microenvironment of cervical cancer: An in vitro study.
abstract: OBJECTIVE
  The fundamental events for cancer progression and metastases include loss of cell adhesion, cell proliferation, anchorage-independent cell growth (evading anoikis), cell migration and cell invasion. All these events leading to cancer progression happen in a favorable nurturing tumor microenvironment. This study was designed to explore the anti-tumor activity of staurosporine (a nonspecific protein kinase inhibitor) in the tumor microenvironment of cervical cancer.
  
  
  METHODS
  The anti-tumor activity of staurosporine was investigated by cell adhesion assay, colony formation assay, apoptosis assay and quantitative real-time polymerase chain reaction (PCR) in cervical cancer cell lines.
  
  
  RESULTS
  The cell adhesion assay showed that staurosporine induces adhesion of cervical cancer cells to the extracellular matrix (ECM) protein fibronectin. The soft agar colony formation assay showed that staurosporine inhibits both the number and size of colony formation in a dose dependent manner and also induces adherent tendency in the cancer cells. Staurosporine also induces prominent apoptosis in single cell suspensions compared to adherent cells. Stroma cell induced transcription of matrix metalloprotease 1 (MMP1) and matrix metalloprotease 2 (MMP2) in cervical cancer cells was inhibited by staurosporine.
  
  
  CONCLUSIONS
  Our results indicate that staurosporine induces anti-tumor response in the cervical tumor microenvironment by inhibiting the fundamental events for cancer progression and metastases. The present study represents an attractive area for further research and opens up new avenues towards the understanding of cervical cancer therapeutics.
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Suresh Singh
authors.initials: SS
authors.lastname: Yadav
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Chandra Bhushan
authors.initials: CB
authors.lastname: Prasad
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Shyam Babu
authors.initials: SB
authors.lastname: Prasad
authors.affiliation: Department of Obstetrics and Gynaecology, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Lakshmi Kant
authors.initials: LK
authors.lastname: Pandey
authors.affiliation: Department of Zoology, Mahila Mahavidyalaya, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Sunita
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Radiotherapy & Radiation Medicine, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Pradhan
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, India. Electronic address: gnarayan@bhu.ac.in.
authors.forename: Gopeshwar
authors.initials: G
authors.lastname: Narayan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002584:Cervix Uteri / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology*; D059016:Tumor Microenvironment / Q000187:drug effects*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1; D019311:Staurosporine
keywords: Anchorage-independent cell growth; Apoptosis; Cell adhesion; Cervical cancer; MMP; Staurosporine