Bacillus thuringiensis as a factory producing parasporin toxins with promising anticancer properties: a review

Bacillus thuringiensis, a facultatively aerobic, endospore-forming Gram-positive bacterium, is widely distributed across diverse natural environments. This bacterium is recognized as a cell factory producing insecticidal Cry (crystalline) toxins, also known as δ-endotoxins. However, during the stationary phase of growth, non-insecticidal B. thuringiensis strains synthesize inclusions composed of precursors of toxins called parasporins, which exhibit selective cytotoxicity toward cancer cells without harming normal cells. To date, six B. thuringiensis parasporins (PS1-PS6) have been identified and categorized into the three-domain toxin type (PS1, PS3, PS6) and the β-pore-forming toxin type (PS2, PS4, PS5). The anticancer activity of parasporins is primarily due to the induction of apoptotic pathways in cancer cells or to the formation of transmembrane pores that lead to necrosis. Among the characterized parasporins, PS2Aa1, PS4Aa1, and PS5Aa1 exhibit the highest anticancer potential, especially against leukemia, cervical, uterine, lung, colon, and hepatocellular cancer cells. Additionally, parasporins have been shown to exert cytotoxic effects on animal-derived cancer cell lines. The discovery of parasporin proteins synthesized by B. thuringiensis that exhibit non-hemolytic and non-insecticidal properties but display selective antitumor effects without harming normal cells underscores their potential biomedical significance and the possibility of novel applications of B. thuringiensis in human and veterinary medicine. Recent studies suggest that the molecular modifications of parasporins, such as conjugation with silver nanoparticles or maltose-binding proteins, represent a promising research direction and may facilitate future advances in anticancer therapy.