Induced G2/M arrest and apoptosis in human epidermoid carcinoma cell lines by semisynthetic drug Ukrain

Anticancer Res. Sep-Oct 2000;20(5A):3163-7.

Abstract

Exposure of ME180 and A431 carcinoma cells to Ukrain (NSC-631570), a novel semisynthetic drug from Chelidonium majus L, results in cell growth inhibition which is concomitant with reversible G2/M cell cycle arrest and apoptosis at doses as low as 7 microM. In contrast, the same drug concentrations were not affective towards normal human keratinocytes. In order to investigate whether cell cycle control mechanisms are effected in response to Ukrain, we analyzed cell cycle distribution and levels of cyclins and cyclin-dependent kinases in drug treated carcinoma cells. We found alterations in levels of mitotic cyclins A and B1, and cyclin-dependent kinases CDK1 and CDK2, after treatment. We also observed an upregulation of CDK inhibitor p27 in both cancer cell lines which may lead to the G2/M cells accumulation.

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Berberine Alkaloids
  • CDC2 Protein Kinase / biosynthesis
  • CDC2-CDC28 Kinases*
  • Carcinoma, Squamous Cell
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • Cyclin A / biosynthesis
  • Cyclin B / biosynthesis
  • Cyclin B1
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / biosynthesis
  • Dose-Response Relationship, Drug
  • G2 Phase
  • Growth Inhibitors / chemical synthesis
  • Growth Inhibitors / pharmacology*
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Microfilament Proteins / biosynthesis
  • Mitosis
  • Muscle Proteins*
  • Phenanthridines
  • Protein Serine-Threonine Kinases / biosynthesis
  • Tumor Cells, Cultured

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Berberine Alkaloids
  • CCNB1 protein, human
  • Ccnb1 protein, mouse
  • Cyclin A
  • Cyclin B
  • Cyclin B1
  • Growth Inhibitors
  • Microfilament Proteins
  • Muscle Proteins
  • Phenanthridines
  • Tagln protein, mouse
  • ukrain
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases