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

Molecules. 2022 Oct 1;27(19):6491. doi: 10.3390/molecules27196491.

Abstract

Due to the lack of chemotherapeutic drugs that selectively affect cervical cancer cells, natural sources such as snake venom are currently being investigated for molecules with antitumor potential. Pllans-II, a phospholipase A2 type-Asp49 from Porthidium lansbergii lansbergii snake venom, induced cell death in a cervical cancer cell line-Ca Ski-related to dysfunction in the ability to resolve endoplasmic reticulum stress, evidenced by sub-expression of genes such as PERK, ERO1 PDIs, HSP70, and CHOP. Western blot analysis validated the last two genes' sub-expression at the protein level. In addition, Pllans-II presented a dose-dependent cytotoxic effect on cancer cells and an insignificant effect on healthy endothelial cells (HUVEC). Additionally, Pllans-II inhibited cancer cells' adhesion and migration capacity, induced cell cycle arrest in the G2/M phase, and induced apoptosis stimulated possibly by the extrinsic route. These results demonstrate for the first time that Pllans-II has an antitumor effect on a squamous epithelial cervical cancer cell line and represents a possible biotechnological tool for designing a prominent antitumor agent.

Keywords: antitumor potential; bioprospecting; phospholipase A2; snake venom; transcriptomic analysis.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Bone Neoplasms*
  • Breast Neoplasms*
  • Carcinoma, Squamous Cell*
  • Cell Line, Tumor
  • Endoplasmic Reticulum Stress
  • Endothelial Cells
  • Female
  • Humans
  • Phospholipases A2 / pharmacology
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / pathology

Substances

  • Antineoplastic Agents
  • Phospholipases A2