Search

Baicalein (BA), one of the major bioactive flavonoids isolated from Scutellariae Radix, possesses various pharmacological activities. The present study aimed to investigate the protective effects of BA on tert‑butyl hydroperoxide (t‑BHP)‑induced hepatotoxicity, and to investigate the potential mechanisms in LO2 cells. BA was demonstrated to possess protective properties against t‑BHP injury in LO2 cells, as evidenced by MTT and lactate dehydrogenase assays. BA significantly prevented t‑BHP‑induced depolarization of mitochondrial membrane potential (MMP), decreased the percentage of apoptotic cells caused by t‑BHP, and prevented intracellular reactive oxygen species (ROS) generation in LO2 cells. Furthermore, BA slightly triggered autophagy in LO2 cells, as evidenced by the elevation of LC3‑II expression, while BA combined treatment with an autophagy inhibitor (chloroquine) or activator (rapamycin) did not alter the hepatoprotective properties. In conclusion, BA may possess a hepatoprotective effect against t‑BHP‑induced liver cell injury, dependent on ROS removal. Therefore, BA may represent a potential drug candidate in protecting hepatotoxicity.

Solasodine, a steroidal alkaloid isolated from solanaceous species, exhibits anticancer activities on several cell lines. This study aimed to explore the antitumor potential of solasodine on ovarian cancer cells. The MTT assay, lactate dehydrogenase release assay, Hoechst 33342 staining, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine staining assay, and Annexin V/PI assay were conducted to investigate the antiproliferation and apoptosis-inducing effects of solasodine. Monodansylcadaverine staining was performed to label the acidic puncta on ovarian cancer HEY cells. A wound healing assay and Transwell assay were carried out to determine whether solasodine elicits an antimetastatic effect on HEY cells. A gelatin zymography assay was applied to detect the enzymatic activities of matrix metalloproteinases. Western blot was employed to examine relevant protein expression. Results revealed that solasodine inhibited cell viabilities in a time- and dose-dependent manner, triggered apoptotic body formation, reduced cell mitochondrial membrane potential, and interfered with autolysosome degradation in ovarian cancer cells. Solasodine also suppressed the migration and invasion of HEY cells by downregulating matrix metalloproteinase expression and activities. This study could be used as a basis for further studies on the molecular mechanisms of the antiproliferation, apoptosis-inducing, autophagy-modifying, and antimetastatic activities of solasodine.

Licochalcone A (LCA), a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, presents obvious anti-cancer effects. In this study, the anti-cancer effects and potential mechanisms of LCA in non-small cell lung cancer (NSCLC) cells were studied. LCA decreased cell viability, increased lactate dehydrogenase release and induced apoptosis in a concentration-dependent manner in NSCLC cells while not in human embryonic lung fibroblast cells. The expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and formation of GFP-LC3 punta, two autophagic markers, were increased after treatment with LCA. LCA-induced LC3-II expression was increased when combined with chloroquine (CQ), while knock-down of autophagy related protein (ATG) 7 or ATG5 reversed LCA-induced LC3-II expression and GFP-LC3 punta formation, suggesting that LCA induced autophagy in NSCLC cells. Inhibition of autophagy could not reverse the LCA-induced cell viability decrease and apoptosis. In addition, LCA increased the expression of endoplasmic reticulum stress related proteins, such as binding immunoglobulin protein and C/EBP homologous protein (CHOP). Knock-down of CHOP reversed LCA-induced cell viability decrease, apoptosis and autophagy. Taken together, LCA-induced autophagic effect is an accompanied phenomenon in NSCLC cells and CHOP is critical for LCA-induced cell viability decrease, apoptosis and autophagy.

Platycodin D, the main saponin isolated from Chinese herb Platycodonis Radix, exhibits anticancer activities against various cancer cell lines. Here we evaluated its anticancer action against human hepatocellular carcinoma cells in vitro and in vivo, and elucidated the relationship between platycodin D-induced apoptosis and autophagy.The viability of human hepatocellular carcinoma BEL-7402 cells was evaluated with MTT assay, and the apoptosis was examined using Annexin V/PI and Hoechst 33342 staining assays. Monodansylcadaverine (MDC) staining was used to label autophagic vacuoles. The proteins were detected using Western blot analysis. For studying its anticancer action in vivo, platycodin D (5 and 10 mg· kg(-1)·d(-1)) was intraperitoneally injected to BEL-7402-bearing mice for 21 days.Platycodin D (5-40 μmol/L) inhibited the cell proliferation in vitro with IC50 values of 37.70±3.99, 24.30±2.30 and 19.70±2.36 μmol/L at 24, 48 and 72 h, respectively. Platycodin D (5-20 μmol/L) dose-dependently increased BEL-7402 cell apoptosis, increased the Bax/Bcl-2 ratio and the levels of cleaved PARP and cleaved caspase-3, and decreased the level of Bcl-2. Furthermore, platycodin D (5-20 μmol/L) induced autophagy in BEL-7402 cells, as evidenced by formation of cytoplasmic vacuoles, increased amounts of LC3-II, and increased numbers of MDC-positive cells. Pretreatment with the autophagy inhibitor chloroquine (5 μmol/L) or BAF (50 nmol/L) significantly enhanced platycodin D-induced proliferation inhibition and apoptosis. Moreover, platycodin D (20 μmol/L) activated the ERK and JNK pathways in BEL-7402 cells, and simultaneous blockage of the two pathways effectively suppressed platycodin D-induced autophagy and enhanced platycodin D-induced apoptosis. In BEL-7402-bearing mice, platycodin D (10 mg·kg(-1)•d(-1)) significantly reduced relative tumor volume with decreased body weight.Platycodin D not only inhibits the proliferation of BEL-7402 cells but also suppresses BEL-7402 xenograft tumor growth. Platycodin D-induced cell proliferation inhibition and apoptosis are amplified by co-treatment with autophagy inhibitors.