Ursolic acid (UA) is a pentacyclic triterpene acid that is present in a wide variety of medicinal herbs and edible plants. This study investigated the effect of UA on apoptosis and proliferation of hepatocellular carcinoma SK-Hep-1 cells. After treatment of SK-Hep-1 cells with different concentrations of UA, we observed that cell viability was reduced in a dose- and time-dependent manner. Furthermore, there was a dose-dependent increase in the percentage of cells in the sub-G1 and G2/M phases, with cells treated with 60 μM showing the highest percentages of cells in those phases. UA-induced chromatin condensation of nuclei was observed by using DAPI staining. The western blot results revealed that exposure to UA was associated with decreased expression of the anti-apoptotic proteins Mcl-1, Bcl-xL, Bcl-2, and TCTP and increased expression of apoptosis-related proteins TNF-α, Fas, FADD, Bax, cleaved caspase-3, caspase-8, caspase-9, and PARP. Immunocytochemistry staining showed that treatment with UA resulted in increased expression of caspase-3. Moreover, exposure to UA resulted in the inhibition of the PI3K/Akt and p38 MAPK signaling pathways. These findings suggest that UA inhibits the proliferation of SK-Hep-1 cells and induces apoptosis.

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor prognosis, largely due to resistance to current radiotherapy and Temozolomide chemotherapy. The constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) is evidenced as a pivotal driver of GBM pathogenesis and therapy resistance, and hence, is a promising GBM drug target. 5-acetyloxy-6,7,8,4′-tetramethoxyflavone (5-AcTMF) is an acetylated derivative of Tangeretin which is known to exert anticancer effects on breast, colon, lung, and multiple myeloma; however, its effect on GBM remains elusive. Herein, we reported that 5-AcTMF suppressed the viability and clonogenicity along with inducing apoptosis in multiple human GBM cell lines. Mechanistic analyses further revealed that 5-AcTMF lowered the levels of Tyrosine 705-phosphorylated STAT3 (p-STAT3), a canonical marker of STAT3 activation, but also dampened p-STAT3 upregulation elicited by Interleukin-6. Notably, ectopic expression of dominant-active STAT3 impeded 5-AcTMF-induced suppression of viability and clonogenicity plus apoptosis induction in GBM cells, confirming the prerequisite of STAT3 blockage for the inhibitory action of 5-AcTMF on GBM cell survival and growth. Additionally, 5-AcTMF impaired the activation of STAT3 upstream kinase JAK2 but also downregulated antiapoptotic BCL-2 and BCL-xL in a STAT3-dependent manner. Moreover, the overexpression of either BCL-2 or BCL-xL abrogated 5-AcTMF-mediated viability reduction and apoptosis induction in GBM cells. Collectively, we, for the first time, revealed the anticancer effect of 5-AcTMF on GBM cells, which was executed via thwarting the JAK2-STAT3-BCL-2/BCL-xL signaling axis. Our findings further implicate the therapeutic potential of 5-AcTMF for GBM treatment.

Ursolic acid (UA), is a kind of triterpene acid that exhibits wide biological properties. In this article, the effects of UA on apoptosis and the proliferation of human hepatoma Huh-7 cells were reported. The MTT results showed that cell viability of Huh-7 was reduced in a concentration and time-dependent effect. In addition, DAPI staining was used to detected condensation of chromatin in nucleus. Apoptotic cell population was examined using Annexin V/PI staining. The results showed that exposure to UA affected extrinsic and intrinsic pathways through, reduced expression of Bcl-2, Mcl-1, and TCTP; increased levels of the apoptotic proteins TNF-α, Fas, FADD, and Bax; and activation of cleaved caspase-3 and PARP. UA also inhibited the p-Akt and p38 MAPK signaling transduction pathways, and increased activity in the p-ERK signaling pathway. Taken together, UA inhibited the cell growth of Huh-7 cells and affected apoptosis, via regulated cellular signaling transduction.

Hinokitiol is a tropolone-related compound isolated from the heartwood of cupressaceous plants. It is known to exhibit various biological functions including antibacterial, antifungal, and antioxidant activities. In the study, we investigated the antitumor activities of hinokitiol against human osteosarcoma cells. The results revealed that hinokitiol treatment inhibited cell viability of human osteosarcoma U-2 OS and MG-63 cells in the MTT assay. Further study revealed that hinokitiol exposure caused cell cycle arrest at the S phase and a DNA damage response with the induction of γ-H2AX foci in both osteosarcoma cell lines. In U-2 OS cells with wild-type tumor suppressor p53, we found that hinokitiol exposure induced p53 expression and cellular senescence, and knockdown of p53 suppressed the senescence. However, in MG-63 cells with mutated p53, a high percentage of cells underwent apoptosis with cleaved-PARP expression and Annexin V staining after hinokitiol treatment. In addition, up-regulated autophagy was observed both in hinokitiol-exposed U-2 OS and MG-63 cells. As the autophagy was suppressed through the autophagy inhibitor chloroquine, hinokitiol-induced senescence in U-2 OS cells was significantly enhanced accompanying more abundant p53 expression. In MG-63 cells, co-treatment of chloroquine increased hinokitiol-induced apoptosis and decreased cell viability of the treated cells. Our data revealed that hinokitiol treatment could result in different cell responses, senescence or apoptosis in osteosarcoma cell lines, and suppression of autophagy could promote these effects. We hypothesize that the analysis of p53 status and co-administration of autophagy inhibitors might provide more precise and efficacious therapies in hinokitiol-related trials for treating osteosarcoma.

Oxidized graphene quantum dots (o-GQDs) alter viability and cell-cycle progression in breast cancer cells, yet the cellular programs underlying these effects remain incompletely defined. We exposed MCF-7 cells to 10 mg/L o-GQD for 72 h and integrated RNA sequencing with quantitative protein-marker, ROS, antioxidant-intervention, proteasome-inhibition, and puromycin-labeling analyses from independent experiments. Transcriptomic analyses showed significant negative enrichment of proliferative and cell-cycle programs (E2F Targets, G2M Checkpoint, MYC Targets V1), with complementary KEGG/Reactome evidence of attenuated estrogen-associated programs. Quantitative Western blotting showed dose-dependent reductions in ERα (to 41.36 ± 13.73% at 10 mg/L), p-RB (to 8.31 ± 10.39%), and Survivin (to 23.97 ± 19.01%), with p-ERK/ERK attenuation and marked γ-H2AX accumulation (345.21 ± 161.39%). The ROS-positive fraction rose from 6.86% to 30.46%; antioxidant co-treatment failed to rescue the phenotype and MG132 did not consistently restore protein markers, arguing against oxidative stress or proteasomal degradation as standalone drivers. Reduced puromycin labeling added a protein-homeostasis readout consistent with reduced nascent protein synthesis. BT-474 and MDA-MB-231 cells showed weaker or different marker responses. Together, these findings define a coordinated MCF-7 response spanning estrogen-associated and cell-cycle programs, survival markers, protein homeostasis, and cell fate.