PS9, Derived from an Aquatic Fungus Virulent Protein, Glycosyl Hydrolase, Arrests MCF-7 Proliferation by Regulating Intracellular Reactive Oxygen Species and Apoptotic Pathways

One of the most commondiseases in women is breast cancer, whichhas the highest death globally. Surgery, chemotherapy, hormone treatments,and radiation are the current treatment options for breast cancer.However, these options have several adverse side effects. Recently,peptide-based drugs have gained attention as anticancer therapy. Studiesreport that peptides from biological toxins such as venom and virulentpathogenic molecules have potential therapeutic effects against multiplediseases, including cancers. This study reports on the invitro anticancer effect of a short peptide, PS9, derivedfrom a virulent protein, glycosyl hydrolase, of an aquatic fungus, Aphanomyces invadans. This peptide arrests MCF-7proliferation by regulating intercellular reactive oxygen species(ROS) and apoptotic pathways. Based on the potential for the anticancereffect of PS9, from the in silico analysis, in vitro analyses using MCF-7 cells were executed. PS9 showeda dose-dependent activity; its IC50 value was 25.27-43.28 mu M at 24 h. The acridine orange/ethidium bromide (AO/EtBr) staining,to establish the status of apoptosis in MCF-7 cells, showed morphologiesfor early and late apoptosis and necrotic cell death. The 2,7-dichlorodihydrofluoresceindiacetate (DCFDA) staining and biochemical analyses showed a significantincrease in reactive oxygen species (ROS). Besides, PS9 has been shownto regulate the caspase-mediated apoptotic pathway. PS9 is nontoxic, in vitro, and in vivo zebrafish larvae.Together, PS9 may have an anticancer effect in vitro.

Automated summary

Breast cancer is a common and deadly disease in women. Current treatment options such as surgery, chemotherapy, hormone treatments, and radiation have adverse side effects. Peptide-based drugs, derived from biological toxins, have shown potential therapeutic effects against various diseases including cancer. This study reports on the invitro anticancer effect of a short peptide, PS9, derived from an aquatic fungus. PS9 inhibited the proliferation of MCF-7 cells by regulating reactive oxygen species (ROS) and apoptotic pathways. It showed dose-dependent activity and is non-toxic in vitro and in vivo zebrafish larvae. PS9 has the potential to be an effective anticancer drug.