# Parasporin-2-Derived Peptide Fragments: Characterization and Synergistic Anticancer Activity with Sacha Inchi and Curcumin

## TL;DR

Researchers tested modified peptides from a cancer-fighting protein and found that combining them with curcumin boosts their anticancer effects, while Sacha inchi may interfere.

## Contribution

This is the first study to explore synergistic effects of Parasporin-2 peptides with curcumin or Sacha inchi, introducing a novel substitution-based strategy for anticancer peptides.

## Key findings

- Modified peptide T104L-G108W showed superior anticancer activity compared to native peptide P102-K11.
- Curcumin-bioconjugated peptides were more effective against cancer cell lines than Sacha inchi combinations.
- Peptide T104L-G108W increased sensitivity in SiHa and HeLa cells, as shown by caspase activation and viability assays.

## Abstract

Cancer remains one of the leading causes of mortality worldwide, underscoring the urgent need for innovative and effective therapeutic strategies. Parasporins, a group of proteins produced by Bacillus thuringiensis, have gained considerable attention due to their selective cytotoxicity toward cancer cells while sparing healthy tissues. Curcumin, a polyphenolic compound from turmeric, and Sacha inchi, an Amazonian seed rich in polyunsaturated fatty acids and bioactive molecules, also exhibit well-documented antioxidant, anti-inflammatory, and antiproliferative properties. The objective of this study was to characterize peptide fragments derived from Parasporin-2 and evaluate their anticancer activity, both individually and in combination with curcumin and Sacha inchi, to determine potential synergistic effects. To achieve this, we conducted in vitro cytotoxicity and antiproliferative assays on human cancer cell lines using peptide fragments, curcumin, and Sacha inchi, alone and in combination, to assess their integrated biological activity and quantify synergism. This is the first study to explore the combined effects of Parasporin-2 peptides with curcumin or Sacha inchi, offering new insights into natural and peptide-based synergistic platforms for potential anticancer therapy.

Background/Objectives: Parasporin PS2Aa1, recently designated as Mpp46Aa1, is recognized for its selective anticancer activity against various human cell lines. In this study, specific regions of the native protein were fragmented, and targeted amino acid substitutions were introduced to improve cytotoxic selectivity and potency. Methods: The modified fragments were evaluated individually and in combination with curcumin, a polyphenol with well-documented anticancer properties, and Sacha inchi-derived matrices, known for their antioxidant and antiproliferative activities. Results: Experimental results demonstrated that the substituted variant designated T104L-G108W exhibited superior anticancer activity compared to the native peptide P102-K11. Synergism assays revealed that curcumin-bioconjugated peptides were more effective against the tested cell lines, whereas combinations with Sacha inchi reduced cytotoxicity, suggesting possible interference in the mechanisms of action. Functional assays, including caspase 3/7 and 9 activation, Annexin V-Cy3 staining, and cell viability analysis with 6-CFDA, confirmed increased sensitivity in SiHa and HeLa cell lines, particularly for peptide T104L-G108W. Conclusions: Collectively, these findings support the effectiveness of a substitution-based strategy in improving parasporin fragments and underscore the therapeutic potential of peptide T104L-G108W as a novel anticancer candidate. Furthermore, this study provides preliminary evidence that natural biomolecules can be optimized through targeted modifications and rational combinations, establishing a framework for the development of sustainable and selective therapeutic approaches in cancer treatment.