Targeted screening of the synergistic components in Artemisia annua L. leading to enhanced antiplasmodial potency of artemisinin based on a "top down" PD-PK approach.

Ethnopharmacological Relevance: Artemisinin (ART) showed enhanced antimalarial potency in the herb Artemisia annua L. (A. annua), from which ART is isolated.

High expression levels of DEF6 predicts a poor prognosis for patients with clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant tumors and early detection contributes to a better prognosis. Finding new biomarkers for the diagnosis or treatment remains meaningful. DEF6 guanine nucleotide exchange factor (DEF6) is upregulated in ccRCC compared to normal controls, but the relationship between DEF6 expression and prognosis in ccRCC is unclear.

Investigation of the component in Artemisia annua L. leading to enhanced antiplasmodial potency of artemisinin via regulation of its metabolism.

Ethnopharmacological Relevance: The chemical matrix of the herb Artemisia annua L. (A. annua), from which artemisinin (QHS) is isolated, can enhance both the bioavailability and efficacy of QHS.

Mogrol represents a novel leukemia therapeutic, via ERK and STAT3 inhibition.

Unlike solid tumors, the primary strategy for leukemia treatment is chemotherapy. However, leukemia chemotherapy is associated with adverse drug effects and drug resistance. Therefore, it is imperative to identify novel agents that effectively treat leukemia while minimizing adverse effects.

Tirapazamine sensitizes hepatocellular carcinoma cells to topoisomerase I inhibitors via cooperative modulation of hypoxia-inducible factor-1α.

Topoisomerase I inhibitors are a class of anticancer drugs with a broad spectrum of clinical activity. However, they have limited efficacy in hepatocellular cancer. Here, we present in vitro and in vivo evidence that the extremely high level of hypoxia-inducible factor-1α (HIF-1α) in hepatocellular carcinoma is intimately correlated with resistance to topoisomerase I inhibitors.

Q6, a novel hypoxia-targeted drug, regulates hypoxia-inducible factor signaling via an autophagy-dependent mechanism in hepatocellular carcinoma.

Tumor hypoxia underlies treatment failure and yields more aggressive and metastatic cancer phenotypes. Although therapeutically targeting these hypoxic environments has been proposed for many years, to date no approaches have shown the therapeutic value to gain regulatory approval. Here, we demonstrated that a novel hypoxia-activated prodrug, Q6, exhibits potent antiproliferative efficacy under hypoxic conditions and induces caspase-dependent apoptosis in 2 hepatocellular carcinoma (HCC) cell lines, with no obvious toxicity being detected in 2 normal liver cell lines.

Synergistic antitumor activity of gemcitabine and ABT-737 in vitro and in vivo through disrupting the interaction of USP9X and Mcl-1.

The Bcl-2 antagonist ABT-737 targets Bcl-2/Bcl-xL, but not Mcl-1, which may confer resistance to this agent in various cancers with high levels of Mcl-1. Here, we showed that the combination of gemcitabine and ABT-737 exhibited synergistic cytotoxicity and induced significant apoptosis in multiple cancer types, including lung, renal, bladder, and prostate cancers. The enhanced apoptosis induced by gemcitabine plus ABT-737 was accompanied by the greater extent of mitochondrial depolarization, caspases-3 activation, and PARP cleavage in 95-D and 5637 cell lines.

Celastrol acts as a potent antimetastatic agent targeting beta1 integrin and inhibiting cell-extracellular matrix adhesion, in part via the p38 mitogen-activated protein kinase pathway.

Malignant tumors remain a significant health threat, with death often occurring as a result of metastasis. Cell adhesion is a crucial step in the metastatic cascade of tumor cells, and interruption of this step is considered to be a logical strategy for prevention and treatment of tumor metastasis. Celastrol [3-hydroxy-24-nor-2-oxo-1(10),3,5,7-friedelatetraen-29-oic acid], a quinone methide triterpene from the medicinal plant Tripterygium wilfordii, possesses antitumor activities, whereas the underlying mechanism(s) remains elusive.