Pllans-II Induces Cell Death in Cervical Cancer Squamous Epithelial Cells via Unfolded Protein Accumulation and

Alejandro Montoya-Gómez1, Nelson Rivera Franco2, Leonel Ives Montealegre-Sanchez1

  • 1Grupo de Nutrición, Facultad de Salud, Universidad del Valle, Cali 760043, Colombia.

Insights

Snake venom compound Pllans-II shows antitumor potential against cervical cancer. It induces cancer cell death by disrupting endoplasmic reticulum stress, inhibiting migration, and causing apoptosis, while sparing healthy cells.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Cervical cancer lacks targeted chemotherapeutic drugs.
  • Natural sources, like snake venom, are explored for novel antitumor compounds.
  • Phospholipase A2 (PLA2) enzymes are investigated for therapeutic potential.

Purpose of the Study:

  • To investigate the antitumor effects of Pllans-II, a PLA2-Asp49 from Porthidium lansbergii lansbergii snake venom, on cervical cancer cells.
  • To elucidate the mechanisms underlying Pllans-II's cytotoxic activity.

Main Methods:

  • Cell viability assays on Ca Ski (cervical cancer) and HUVEC (healthy endothelial) cells.
  • Gene expression analysis (PERK, ERO1 PDIs, HSP70, CHOP) and Western blot.
  • Assessment of cell adhesion, migration, cell cycle, and apoptosis.

Main Results:

  • Pllans-II induced cell death in Ca Ski cells by impairing endoplasmic reticulum stress resolution.
  • Downregulation of PERK, ERO1 PDIs, HSP70, and CHOP genes and proteins was observed.
  • Pllans-II exhibited dose-dependent cytotoxicity against cancer cells with minimal effect on HUVECs.
  • Inhibition of cancer cell adhesion and migration, G2/M phase arrest, and apoptosis induction were noted.

Conclusions:

  • Pllans-II demonstrates significant antitumor activity against squamous epithelial cervical cancer cells.
  • Pllans-II's mechanism involves endoplasmic reticulum stress dysfunction and apoptosis induction.
  • This snake venom component shows promise as a potential biotechnological tool for developing novel cervical cancer therapeutics.

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