Platycodin D2

Platycodin D2 is an orally active triterpenoid saponin found in Platycodon grandiflorum. Platycodin D2 induces mitophagy in cancer cells through NIX, thereby activating the P21/CyclinA2 pathway and promoting cell senescence. Platycodin D2 induces mitochondrial dysfunction, enhances autophagy, inhibits hepatocellular carcinoma cell proliferation, and exhibits anti-tumor activity against multiple cancer cell types. Platycodin D2 promotes mRNA expression of T-bet, GATA-3, Th1 cytokines IL-2 and IFN-γ, and Th2 cytokines IL-4 and IL-10, enhances splenocyte proliferation, and acts as a vaccine adjuvant with low rabbit red blood cell hemolytic activity. Platycodin D2 induces mitochondrial ROS production, incomplete autophagy, and ferroptosis to inhibit breast cancer cell proliferation. Platycodin D2 can be used for the research of cancer, inflammation and immunology^[1][2][3]. In Vitro:Platycodin D2 (1-100 μM; 48 h) specifically inhibits proliferation of Huh-7, MHCC97H, HCCLM3, HepG-2, SK-Hep1, and Huh-6 HCC cells with an IC₅₀ of 10.2-12.7 μM, while having no significant cytotoxic effect on THLE-2 and L02 normal liver cells (IC₅₀ >200 μM)^[1].
Platycodin D2 (10 μM; 48 h) does not significantly induce apoptosis in Huh-7 or HCCLM3 HCC cells^[1].
Platycodin D2 (10 μM; 24-48 h) induces robust autophagy in Huh-7 and HCCLM3 HCC cells, as evidenced by increased LC3 puncta formation, elevated autophagic flux, autophagolysosome formation, and altered expression of autophagy-related proteins, without affecting apoptosis-related proteins^[1].
Platycodin D2 (5, 10 μM; 48 h) induces mitochondrial dysfunction in Huh-7 and HCCLM3 HCC cells, evidenced by increased ROS production, reduced mitochondrial membrane potential, and selective mitophagy via LC3 co-localization with damaged mitochondria^[1].
Platycodin D2 (10 μM; 48 h) induces mitophagy in HCCLM3 HCC cells via NIX, as silencing NIX abrogates PD2's effects on autophagy, cell viability, mitochondrial function, and downstream P21/CyclinA2 expression^[1].
Platycodin D2 (10 μM; 48 h) induces G2/M phase arrest and senescence in Huh-7 and HCCLM3 HCC cells, evidenced by altered cell cycle distribution, upregulated SASP gene expression, shifted expression of senescence-related proteins, increased β-galactosidase activity, reduced Lamin B1 levels, and nuclear γ-H2A.X aggregation^[1].
Platycodin D2 (3.906-125 μg/mL; 30 min) exhibits haemolytic activity against 0.5% rabbit red blood cell suspensions with an HD₅₀ of 18.57 μg/mL^[2].
Platycodin D2 (0.0016-1.0 μg/mL; 16 h) significantly enhances mRNA expression of Th1 (IL-2, IFN-γ, T-bet) and Th2 (IL-4, IL-10, GATA-3) cytokines and transcription factors in Con A-stimulated naive ICR mouse splenocytes^[2].
Platycodin D2 (5-50 μM; 48 h) potently inhibits the proliferation of MCF7, SKBR3, and Hs578T breast cancer cells with IC₅₀ values of 14.62 μM, 29.60 μM, and 5.24 μM, respectively, after 48 h of incubation^[3].
Platycodin D2 (5-50 μM; 48 h) blocks autophagy flux in MCF7, SKBR3, and Hs578T breast cancer cells by increasing LC3II/I and p62 expression while decreasing Syntaxin 17, SNAP29, VAMP8, and Lamp2b expression after 48 h of incubation^[3].
Platycodin D2 (5-50 μM; 48 h) induces ferroptosis in MCF7, SKBR3, and Hs578T breast cancer cells by decreasing SLC7A11, GSH and GPX4 expression after 48 h of incubation^[3].
Platycodin D2 (5-50 μM; 48 h) increases intracellular ferrous ion levels in MCF7, SKBR3, and Hs578T breast cancer cells after 48 h of incubation, a hallmark of ferroptosis^[3].
Platycodin D2 (5-50 μM; 48 h) upregulates mitochondrial outer membrane protein TOM20 expression in MCF7, SKBR3, and Hs578T breast cancer cells after 48 h of incubation, indicating mitochondrial damage^[3].
Platycodin D2 (5-50 μM; 48 h) increases intracellular MDA levels in MCF7, SKBR3, and Hs578T breast cancer cells after 48 h of incubation, indicating enhanced lipid peroxidation associated with ferroptosis^[3].
Platycodin D2 (5-50 μM; 48 h) decreases intracellular SOD levels in MCF7, SKBR3, and Hs578T breast cancer cells after 48 h of incubation, reducing antioxidant capacity and promoting ferroptosis^[3].
Platycodin D2 (5-50 μM; 48 h) increases mitochondrial ROS production and reduces mitochondrial membrane potential in MCF7, SKBR3, and Hs578T breast cancer cells after 48 h of incubation, contributing to mitochondrial damage^[3]. In Vivo:Platycodin D2 (5-10 mg/kg; intratumoral injection; once every 3 days; 4 doses) significantly inhibits HCC tumor growth in female BALB/c nude mice in vivo in a dose-dependent manner, with 10 mg/kg achieving near-complete tumor volume reduction, and induces mitophagy and cell senescence via upregulation of LC3-II, NIX, and P21 and downregulation of Cyclin A2^[1].
Platycodin D2 (25-100 μg; s.c.; on Day 1 and Day 15) elicits balanced Th1 and Th2 immune responses in OVA (HY-W250978)-immunized ICR mice, significantly enhancing splenocyte proliferation, OVA-specific antibody titers at tested doses^[2].
Platycodin D2 (2.5-5 mg/kg; i.g.; once every 2 days; 5 total doses) significantly inhibits breast cancer tumor growth in nude mice, with the 5 mg/kg dose reducing tumor volume by 80.5%, and mediates this effect via autophagy flux blockage and ferroptosis^[3].