Wasp venom peptide improves the proapoptotic activity of alendronate sodium in A549 lung cancer cells

PLoS One. 2022 Feb 24;17(2):e0264093. doi: 10.1371/journal.pone.0264093. eCollection 2022.

Abstract

Background: Lung cancer in men and women is considered the leading cause for cancer-related mortality worldwide. Anti-cancer peptides represent a potential untapped reservoir of effective cancer therapy.

Methodology: Box-Behnken response surface design was applied for formulating Alendronate sodium (ALS)-mastoparan peptide (MP) nanoconjugates using Design-Expert software. The optimization process aimed at minimizing the size of the prepared ALS-MP nanoconjugates. ALS-MP nanoconjugates' particle size, encapsulation efficiency and the release profile were determined. Cytotoxicity, cell cycle, annexin V staining and caspase 3 analyses on A549 cells were carried out for the optimized formula.

Results: The results revealed that the optimized formula was of 134.91±5.1 nm particle size. The novel ALS-MP demonstrated the lowest IC50 (1.3 ± 0.34 μM) in comparison to ALS-Raw (37.6 ± 1.79 μM). Thus, the results indicated that when optimized ALS-MP nanoconjugate was used, the IC50 of ALS was also reduced by half. Cell cycle analysis demonstrated a significantly higher percentage of cells in the G2-M phase following the treatment with optimized ALS-MP nanoconjugates.

Conclusion: The optimized ALS-MP formula had significantly improved the parameters related to the cytotoxic activity towards A549 cells, compared to control, MP and ALS-Raw.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Alendronate / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Lung Neoplasms / drug therapy*
  • Nanoconjugates / therapeutic use*
  • Particle Size
  • Wasp Venoms / pharmacology*

Substances

  • Intercellular Signaling Peptides and Proteins
  • Nanoconjugates
  • Wasp Venoms
  • mastoparan
  • Caspase 3
  • Alendronate

Grants and funding

This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no. (RG-10-166-42). The authors, therefore, acknowledge with thanks DSR for technical and financial support. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.