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Published on: February 9, 2024
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.
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.
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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