T-cell-originated protein kinase (TOPK) is highly expressed in several cancer cells and promotes tumorigenesis and progression, and therefore, it is an important target for drug treatment of tumor. Pantoprazole (PPZ) was identified to be a TOPK inhibitor from FDA-approved drug database by structure based virtual ligand screening. Herein, the data indicated that pantoprazole inhibited TOPK activities by directly binding with TOPK in vitro and in vivo. Ex vivo studies showed that pantoprazole inhibited TOPK activities in JB6 Cl41 cells and HCT 116 colorectal cancer cells. Moreover, knockdown of TOPK in HCT 116 cells decreased their sensitivities to pantoprazole. Results of an in vivo study demonstrated that i.p. injection of pantoprazole in HCT 116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after pantoprazole treatment. In short, pantoprazole can suppress growth of colorectal cancer cells as a TOPK inhibitor both in vitro and in vivo.

No abstract

Gastric cancer is a leading cause of cancer‑associated mortality worldwide. In studies on the mechanisms of antigastric cancer drugs, autophagy and endoplasmic reticulum (ER) stress have been demonstrated to serve an active role in gastric cancer. The organic extract of Periplaneta americana (also termed American Cockroach), which is named Kangfuxin (KFX) in China, has been used clinically as a traditional Chinese medicine against disorders, including stomach bleeding, gastric ulcers, tuberculosis, burns and trauma. However, the role of KFX and its mechanism in gastric cancer remains to be elucidated. The present study aimed to determine the effects of KFX in vitro against cultured the human carcinoma SGC‑7901 cell line, and to explore the potential mechanism of the anticancer effects of KFX in gastric cancer. SGC‑7901 cells were treated with different concentrations of KFX for varying amounts of time. As a result, KFX treatment decreased the ratio of apoptosis regulators Bcl‑2/Bax, activated ER stress and induced significant apoptosis in SGC‑7901 cells. Furthermore, KFX was able to restore the ER stress activation blocked by 4‑phenylbutyrate. In addition, KFX activated autophagy in SGC‑7901 cells. These results demonstrated that ER stress, autophagy and the apoptosis‑inducing effects of KFX in SGC‑7901 cells may achieve promising anticancer effects in numerous other types of cancer. In particular, ER stress may serve an essential role in KFX‑induced anticancer effects on gastric carcinoma and a secondary role in autophagy.

No abstract

No abstract