Polysaccharides from perilla (Perilla frutescens L.) seed induce mitochondrial apoptosis in HCT-116 cells via BID - BAX axis

Two homogeneous polysaccharides, PFSP-1 and PFSP-3, were isolated from perilla ( Perilla frutescens L.) seeds (PFSP) and exhibited significant structural differences. Molecular weights of PFSP-1 and PFSP-3 were 3.58 × 10 4 Da and 1.04 × 10 7 Da, respectively. Monosaccharide composition analysis indicated that PFSP-1 consisted of fucose, glucose, and galactose in a molar ratio of 1.36:1.94:1, whereas PFSP-3 was composed of fucose, xylose, glucose, and galactose at a ratio of 3.63:1.21:19.62:1. Morphological observations revealed that PFSP-1 displayed irregular flocculent formations with smooth surfaces, while PFSP-3 showed continuous sheet-like structures. A comparison of bioactivity revealed that PFSP-1, but not PFSP-3, significantly inhibited the proliferation of HCT-116 colon cancer cells. PFSP-1 potently induced apoptosis as evidenced by increased TUNEL positivity, caspase-9/3 activation, and mitochondrial membrane potential collapse. Transcriptomics and validation identified BID and BAX as key mediators. Further validation confirmed that PFSP-1 promoted BID expression, facilitated BAX activation, and triggered mitochondrial dysfunction, ultimately leading to the execution of apoptosis via the caspase-9/caspase-3 cascade. These findings collectively demonstrate that structural variations, particularly in monosaccharide composition and molecular architecture, critically govern the differential anti-colon cancer activity of perilla seed polysaccharides. • PFSP-1 and PFSP-3 were homogeneous polysaccharides purified from perilla seeds. • PFSP-1 showed higher pro-apoptotic activity than PFSP-3 against HCT-116 cells. • PFSP-1 induced mitochondrial apoptosis by activating BID-BAX axis. • Structural difference might explain the differential anti-colon cancer efficacy.