A novel antitumor peptide from silkworm pupae (Bombyx mori): Purification, characterization, and mechanism

Bioactive peptide Tyr-Ala-Ser-Pro-Val-His (YASPVH) was purified from silkworm pupa protein enzymatic hydrolysates, and exhibited potent antiproliferative activity against breast cancer HCC-1937 cells. Besides, YASPVH induced G1 phase cell cycle arrest and suppressed HCC-1937 cell migration and invasion. YASPVH also triggered mitochondrial dysfunction, characterized by membrane potential depolarization and reactive oxygen species (ROS) accumulation, ultimately inducing mitochondrial apoptosis via the Bcl-2/Bax/caspase-3 pathway. Additionally, YASPVH promoted excessive intracellular ROS accumulation, leading to endoplasmic reticulum (ER) stress. This was evidenced by significantly elevated cytosolic Ca 2+ levels and upregulation of ER stress markers PERK, ATF4, and CHOP. YASPVH furthermore inhibited the epithelial-mesenchymal transition process (EMT) by promoting E-cadherin expression while suppressing Vimentin and N-cadherin expression. Collectively, these results demonstrate that YASPVH exerts its antitumor effect by inhibiting proliferation and metastasis, and inducing apoptosis in HCC-1937 cells. This study identifies YASPVH as a promising candidate and provides a novel strategy for breast cancer treatment. • A novel peptide Tyr-Ala-Ser-Pro-Val-His (YASPVH) was purified from silkworm pupa protein enzymatic hydrolysates. • YASPVH exhibited potent antiproliferative activity and antimetastatic effect on HCC-1937 cells. • YASPVH induced HCC-1937 cell apoptosis via activation of the mitochondrial dysfunction pathway. • YASPVH induced HCC-1937 cell apoptosis via endoplasmic reticulum (ER) stress pathway.