RESUMEN
Gastric cancer (GC) is one of the most common malignant tumors worldwide. Thus, the development of safe and effective therapeutic compounds for GC treatment is urgently required. Here, we aimed to examine the role of picropodophyllin (PPP), a compound extracted from the rhizome of Dysosma versipellis (Hance) M. Cheng ex Ying, on the proliferation of GC cells. Our study revealed that PPP inhibits the proliferation of GC cells in a dose-dependent manner by inducing apoptosis. Moreover, our study elucidated that PPP suppresses the growth of GC tumor xenografts with no side effects of observable toxicity. Mechanistically, PPP exerts its effects by blocking the AKT/mammalian target of rapamycin (mTOR) signaling pathway; these effects are markedly abrogated by the overexpression of constitutively active AKT. Furthermore, drug affinity responsive target stability (DARTS) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) revealed that heat shock protein 90 (HSP90) may be a potential target of PPP. Surface plasmon resonance and immunoprecipitation assay validated that PPP directly targets HSP90 and disrupts the binding of HSP90 to AKT, thereby suppressing GC cell proliferation. Thus, our study revealed that PPP may be a promising therapeutic compound for GC treatment.
RESUMEN
Tongue squamous cell carcinoma (TSCC) is the most widespread and invasive subtype of oral cancer with high recurrence rates. Ailanthone (AIL) is an active ingredient in the plant extracts of Ailanthus altissima (Mill.) Swingle. Here, we showed that AIL inhibited the proliferation of human TSCC, the cell viability of Cal-27 and Tca8113 was significantly decreased after AIL treatment for 24 h. Hoechst 33258 staining demonstrated apoptotic characteristics (such as chromatin aggregation) after AIL treatment. The ratio of early- and late-apoptotic cells in AIL-treated Cal-27 and TCA8113 cells increased remarkably when compared with the control group. Bcl-2/Bax ratio and the levels of PARP1, caspase-9, and caspase-3 decreased after AIL treatment, accompanied by significant increase of cleaved PARP1, cleaved caspase-9, and caspase-3 in Cal-27 and TCA8113 cells. Meanwhile, AIL led to Cal-27 cell cycle arrest at G2/M phase. Western blot implied decreased levels of CDK1 and cyclin B1 after AIL treatment. The level of phospho-PI3K p55 subunit and p-Akt were significantly downregulated by AIL in both Cal-27 and TCA8113 cells. These findings implied the potential applications of AIL in the treatment of human TSCC.
RESUMEN
Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.