Bioactive compounds from Perilla frutescens modulate multiple cell death pathways and signaling networks in cancer therapy

Abstract

Perilla frutescens, an edible medicinal plant from East Asia, produces diverse bioactive phytochemicals with anticancer activity, including perillaldehyde (PAH), rosmarinic acid (RA), luteolin, apigenin, and alpha-linolenic acid (ALA). These compounds exert multi-target anticancer effects through apoptosis, autophagy, and ferroptosis. PAH triggers ferroptosis in gastric cancer via the System Xc-/GSH/GPX4 axis and P62-Keap1-Nrf2 pathway, while inducing protective autophagy in colorectal cancer through SRD5A1 and PI3K/AKT modulation. RA directly binds KRAS(G12C) and suppresses NSCLC via KRAS/AKT/ERK, and inhibits stress-induced TNBC metastasis through Src inactivation. Perilla leaf extracts activate Hippo-YAP/TAZ signaling in breast cancer. ALA-rich perilla seed oil (PSO) mitigates tumorigenesis in colitis-associated colorectal cancer models and restores gut microbial homeostasis. This review synthesizes current molecular evidence on perilla compounds in cancer therapy, focusing on apoptosis-autophagy-ferroptosis crosstalk. The multi-target characteristics position perilla-derived compounds as adjuvant cancer therapy candidates, though bioavailability and clinical translation still challenges remain.