Piperlongumine inhibits migration and proliferation of castration-resistant prostate cancer cells via triggering persistent DNA damage.

BACKGROUND: Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among men diagnosed with prostate cancer. Piperlongumine (PL) is a novel potential anticancer agent that has been demonstrated to exhibit anticancer efficacy against prostate cancer cells. However, the effects of PL on DNA damage and repair against CRPC have remained unclear. The aim of this study was to further explore the anticancer activity and mechanisms of action of PL against CRPC in terms of DNA damage and repair processes. METHODS: The effect of PL on CRPC was evaluated by MTT assay, long-term cell proliferation, reactive oxygen species assay, western blot assay, flow cytometry assay (annexin V/PI staining), ß-gal staining assay and DAPI staining assay. The capacity of PL to inhibit the invasion and migration of CRPC cells was assessed by scratch-wound assay, cell adhesion assay, transwell assay and immunofluorescence (IF) assay. The effect of PL on DNA damage and repair was determined via IF assay and comet assay. RESULTS: The results showed that PL exhibited stronger anticancer activity against CRPC compared to that of taxol, cisplatin (DDP), doxorubicin (Dox), or 5-Fluorouracil (5-FU), with fewer side effects in normal cells. Importantly, PL treatment significantly decreased cell adhesion to the extracellular matrix and inhibited the migration of CRPC cells through affecting the expression and distribution of focal adhesion kinase (FAK), leading to concentration-dependent inhibition of CRPC cell proliferation and concomitantly increased cell death. Moreover, PL treatment triggered persistent DNA damage and provoked strong DNA damage responses in CRPC cells. CONCLUSION: Collectively, our findings demonstrate that PL potently inhibited proliferation, migration, and invasion of CRPC cells and that these potent anticancer effects were potentially achieved via triggering persistent DNA damage in CRPC cells.

Preliminary study on the clinical and pathological relevance of gastric hepatoid adenocarcinoma.

OBJECTIVE: To appraise the histological characteristics and clinical features of gastric hepatoid adenocarcinoma (GHAC) and their relevance with prognosis. METHODS: From January 2001 to December 2003, six patients were diagnosed and confirmed pathologically in Ruijin Hospital as having a gastric hepatoid carcinoma. All these six patients, together with 30 randomly selected patients with gastric poorly differentiated adenocarcinoma (GPDA) and 30 with a primary hepatocellular carcinoma (HCC) who served as controls, were studied and analyzed clinically, histologically and immunohistologically. RESULTS: The average age of the six patients with GHAC was 66.8 years, and their serum alpha fetoprotein (AFP) level was 84-2230 ng/mL. Of these six patients, two had a recurrence of cancer and two had liver metastasis. Their average survival period was 17 months. Morphologically, the histological appearance was similar to that of HCC, with glycogen granules and hyaline globules arranged in a solid or trabecular pattern and an abundance of blood vessels and sinusoids, while blood vessel or lymphatic invasion were more often seen. Immunohistological staining showed that the tumor cells were positive for AFP and negative for Hepatocyte paraffin 1 (HepPar1), and the tumor cells were separated by CD34-positive blood vessels into a small trabecular pattern. The GPDA had a solid nest or diffuse distribution pattern and was negative for both AFP and HepPar1. In the HCC, the histological feature was manifested as solid, small and large trabecular patterns with abundance of blood vessels and sinusoids; immunohistochemical staining showed the tumor cells were positive for HepPar1. CONCLUSION: Serum AFP-positive GHAC occurred more frequently in older patients with higher rates of recurrence and liver metastasis and a poor prognosis. Histologically, GHAC was similar to HCC. The tumor cells that were positive for AFP but negative for HerPar1 could be used to differentiate with GPDA (both AFP and HerPar1 negative) and primary HCC (most AFP and HerPar1 positive).