Erianin curbs prostate cancer growth in mice and dampens STAT3 signaling

A preclinical study found that erianin, a small benzyl compound with previously reported anticancer activity, reduced prostate cancer cell growth and movement in laboratory experiments and lowered tumor burden in mice. The treatment also suppressed phosphorylation of signal transducer and activator of transcription 3, or STAT3, and reduced two downstream proteins associated with proliferative and invasive tumor behavior. The results suggest that reduced STAT3 signaling accompanies erianin’s antitumor effects, but they do not establish that STAT3 is a direct molecular target or that its inhibition is required for those effects.

The researchers screened 48 compounds with potential antitumor activity in three prostate cancer cell lines: human PC-3 and 22RV1 cells and mouse RM-1 cells. Erianin produced the strongest overall inhibition of cell viability among the candidates and was then advanced into more detailed functional experiments. Its reported half-maximal inhibitory concentrations were 0.592 micromolar in PC-3 cells, 1.985 micromolar in 22RV1 cells and 0.442 micromolar in RM-1 cells after 24 hours of exposure. In PC-3 and RM-1 cultures, these values were lower than those reported for docetaxel, the study’s positive control, although such comparisons are limited to the particular cell lines, exposure times and assays used.

Additional experiments indicated that erianin affected more than short-term metabolic viability. Concentrations of 0.04, 0.4 and 4 micromolar reduced colony formation in a concentration-dependent manner, a result consistent with an effect on the ability of surviving cells to proliferate. The compound also decreased wound closure in scratch assays of confluent PC-3, 22RV1 and RM-1 monolayers and lowered the number of cells crossing Matrigel-coated membranes in Transwell invasion assays. These assays model migration and invasion under laboratory conditions, but they do not reproduce the full complexity of tumor growth, metastasis or immunity in a patient.

To investigate how erianin might produce these effects, the team combined computational target prediction with two public prostate cancer gene-expression datasets. The researchers intersected genes predicted to be associated with erianin with differentially expressed genes in the datasets, identifying 27 potential shared targets. Pathway analysis pointed to processes involving cell proliferation and adhesion, while protein-protein interaction analysis placed STAT3 at the center of the resulting network. Molecular docking then produced a predicted erianin pose near the SH2 domain of STAT3, adjacent to the Tyr705 phosphorylation site, with a calculated binding energy of −7.1 kilocalories per mole and a hydrophobic interaction involving leucine 618. Docking is a computational prediction rather than direct evidence of binding in living cells.

Protein analyses in the cultured cells provided experimental support for the proposed pathway. Erianin significantly reduced phosphorylated STAT3 at Tyr705 in PC-3, 22RV1 and RM-1 cells while leaving total STAT3 protein largely unchanged. It also reduced MMP-9 protein in all three cell lines. The c-Myc protein level declined significantly in PC-3 and RM-1 cells, while the downward trend in 22RV1 cells was not statistically significant. The measurements are consistent with attenuation of STAT3 signaling, because Tyr705 phosphorylation is closely linked to STAT3 activation and the examined downstream proteins participate in transcriptional programs associated with proliferation, migration and invasion.

The researchers next tested erianin in 30 male C57BL/6N mice bearing subcutaneously implanted RM-1 tumors. After random assignment, six animals per group received saline, erianin at 10, 20 or 40 milligrams per kilogram, or docetaxel at 10 milligrams per kilogram. Erianin was injected intraperitoneally each day, while docetaxel was administered weekly. Over the treatment period, the erianin groups had lower mean estimated tumor volumes than controls. At the experimental endpoint on day 17, tumor weights were significantly lower in every erianin group, and the 20-milligram-per-kilogram group showed the strongest tumor suppression. The tumor-growth curves were presented descriptively rather than subjected to inferential statistical analysis, and the study did not establish an optimal dose or a linear relationship between dose and efficacy.

Tissue analysis showed that erianin-treated tumors contained less phosphorylated STAT3, c-Myc and MMP-9 than control tumors, connecting the molecular changes observed in culture with the mouse experiment. Preliminary safety assessments also found no obvious histopathological changes in the heart, liver, spleen, lungs or kidneys. Serum aspartate aminotransferase, blood urea nitrogen and creatinine did not show significant abnormalities across the dose groups. Alanine aminotransferase increased slightly in the erianin-treated animals but remained within the stated normal range for healthy mice, while platelet counts were also slightly lower but within the reference interval. These observations describe tolerability over the tested 17-day regimen and do not establish the compound’s safety during prolonged exposure.

Several important limitations constrain the conclusions. First, the association between lower STAT3 activity and antitumor effects remains correlational. Reduced Tyr705 phosphorylation could reflect direct interaction with STAT3, but it could also arise from changes in upstream kinases, phosphatases or other signaling regulators. The investigators did not perform target-engagement assays or rescue and loss-of-function experiments that would determine whether STAT3 inhibition is necessary for erianin’s effects. The unexpected animal results further complicate interpretation: tumor suppression was greater at 20 milligrams per kilogram than at 40 milligrams per kilogram, but pharmacokinetic exposure, formulation stability and detailed dose-related toxicity were not assessed, so the basis of that non-monotonic pattern remains unknown.

Translation to human prostate cancer is also uncertain because the study used two human cell lines and one mouse line, together with a subcutaneous mouse tumor model. These systems do not fully reproduce the androgen-receptor states, immune environments, metastatic spread or treatment resistance found in human disease. The authors note that additional work with androgen-receptor-positive and androgen-receptor-negative human models, organoids, patient-derived systems, and clinically relevant metastatic or resistant cancers will be needed. Pharmacokinetic investigations and comprehensive toxicology would also be required. The study therefore identifies erianin as a promising candidate for further preclinical evaluation in prostate cancer, rather than as an established treatment or proof that direct STAT3 targeting accounts for its activity.

Subject of Research: Erianin’s effects on prostate cancer cells, mouse tumors, and STAT3 signaling in preclinical experiments

Article Title: Erianin suppresses prostate cancer progression and attenuates STAT3 signaling

Article References: Yue, Z., Zhao, Y., Wang, J., Wang, F., Wang, M., Li, Z., Li, Y., & Li, M. (2026). Erianin suppresses prostate cancer progression and attenuates STAT3 signaling. Frontiers in Oncology, 16, Article 1975408. https://doi.org/10.3389/fonc.2026.1975408

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1975408

Keywords: erianin, prostate cancer, STAT3, tumor growth, drug screening, cell migration, cancer invasion, mouse model, network pharmacology, molecular docking, suppresses, prostate