Leaf Extract of Nerium oleander L. Inhibits Cell Proliferation, Migration and Arrest of Cell Cycle at G2/M Phase in HeLa Cervical Cancer Cell

Anticancer Agents Med Chem. 2021;21(5):649-657. doi: 10.2174/1871520620666200811121400.


Background: Cervical cancer is one of the most common gynaecological malignant tumors reported in women. Although a number of early screening and treatment options are available, mortality due to cervical cancer remains high. Nerium oleander L. is a potential medicinal plant that possesses a wide spectrum of pharmacological and physiological activities including anticancer activities.

Objective: This study aims to evaluate the antiproliferative activity, inhibition of cell migration and cell cycle arrest by the chloroform extract of leaves of Nerium Oleander L. in HeLa cervical cancer cells. The chloroform extract of Catharanthus roseus which contains anti-cancer compounds, Vinblastin and Vincristin, was used as a positive control for this study.

Methods: The chloroform extracts of Nerium oleander L. and Catharanthus roseus were prepared using the standard protocol. The cytotoxic effects were studied by MTT assay. Cell migration was studied by in vitro scratch assay. Analysis of the cell cycle was carried out by Propidium iodide staining and Flow Cytometry. The expression level of various proteins was evaluated by immunocytochemistry.

Results: In this study, we showed that the leaf extract of Nerium oleander inhibited the growth of HeLa cervical cancer cells in culture and inhibited cell migration. Besides, it arrested the cell cycle at the G2/M phase. The Epidermal Growth Factor Receptor (EGFR) expression and phosphorylated p-Rb (Ser 780) level were significantly downregulated by leaf extract of Nerium oleander.

Conclusion: The extract of Nerium oleander L. contains potential bioactive compounds that inhibit HeLa cell proliferation, cell migration and arrest cell cycle at the G2/M phase.

Keywords: G2/M phase arrest; HeLa cells; MTT assay; Nerium oleander; antioxidant; cell migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Biphenyl Compounds / antagonists & inhibitors
  • Cell Cycle Checkpoints / drug effects*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Nerium / chemistry*
  • Picrates / antagonists & inhibitors
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Structure-Activity Relationship
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Biphenyl Compounds
  • Picrates
  • Plant Extracts
  • 1,1-diphenyl-2-picrylhydrazyl