title: Syringic acid from Tamarix aucheriana possesses antimitogenic and chemo-sensitizing activities in human colorectal cancer cells.
abstract: BACKGROUND
  For its variety of biological activities, Tamarix aucheriana (Decne.) Baum. (Tamaricaceae) has an extensive history as a traditional Arab medicine.
  
  
  OBJECTIVE
  Antimitogenic and chemo-sensitizing activities of syringic acid (SA) were studied against human colorectal cancer.
  
  
  METHODS
  Chromatographic and spectral data were used for the isolation and identification of SA. MTT, flow cytometry, in vitro invasion and angiogenesis assays, fluoremetry, ELISA and Real Time qPCR were used to test antimitogenic and chemo-sensitizing activities of SA, cell cycle, apoptosis, proteasome and NFκB-DNA-binding activities, cancer cell invasion and angiogenesis, and expression of cell cycle/apoptosis-related genes.
  
  
  RESULTS
  SA showed a time- and dose-dependent (IC₅₀ = 0.95-1.2 mg mL⁻¹) antimitogenic effect against cancer cells with little cytotoxicity on normal fibroblasts (≤20%). SA-altered cell cycle (S/G2-M or G1/G2-M phases) in a time-dependent manner, induced apoptosis, inhibited DNA-binding activity of NFκB (p ≤ 0.0001), chymotrypsin-like/PGPH (peptidyl-glutamyl peptide-hydrolyzing) (p ≤ 0.0001) and the trypsin-like (p ≤ 0.002) activities of 26S proteasome and angiogenesis. SA also differentially sensitized cancer cells to standard chemotherapies with a marked increase in their sensitivity to camptothecin (500-fold), 5FU (20,000-fold), doxorubicin (210-fold), taxol (3134-fold), vinblastine (1000-fold), vincristine (130-fold) and amsacrine (107-fold) compared to standard drugs alone.
  
  
  CONCLUSIONS
  SA exerted its chemotherapeutic and chemo-sensitizing effects through an array of mechanisms including cell-cycle arrest, apoptosis induction, inhibition of cell proliferation, cell migration, angiogenesis, NFκB DNA-binding and proteasome activities.
  
  
  CONCLUSIONS
  These results demonstrate the potential of SA as an antimitogenic and chemo-sensitizing agent for human colorectal cancer.
authors.affiliation: Department of Biological Sciences, Faculty of Science, Faculty of Medicine, Kuwait University, Safat, Kuwait. abazams@yahoo.com
authors.forename: Mohamed-Salah
authors.initials: MS
authors.lastname: Abaza
authors.forename: Raja'a
authors.initials: R
authors.lastname: Al-Attiyah
authors.forename: Radhika
authors.initials: R
authors.lastname: Bhardwaj
authors.forename: Ghaneim
authors.initials: G
authors.lastname: Abbadi
authors.forename: Mathew
authors.initials: M
authors.lastname: Koyippally
authors.forename: Mohammad
authors.initials: M
authors.lastname: Afzal
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology; D050256:Antimitotic Agents / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D020834:Ethnopharmacology; D005707:Gallic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007730:Kuwait; D008519:Medicine, Traditional; D008938:Mitosis / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D035261:Plant Components, Aerial / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology; D032363:Tamaricaceae / Q000737:chemistry*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D050256:Antimitotic Agents; D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D061988:Proteasome Inhibitors; C498143:RELA protein, human; D051996:Transcription Factor RelA; D005707:Gallic Acid; C001945:syringic acid; D046988:Proteasome Endopeptidase Complex