CDC20 associated with cancer metastasis and novel mushroom­derived CDC20 inhibitors with antimetastatic activity.

ABSTRACT

Aberrant expression of cell division cycle 20 (CDC20) is associated with malignant progression and poor prognosis in various types of cancer. The development of specific CDC20 inhibitors may be a novel strategy for the treatment of cancer with elevated expression of CDC20. The aim of the current study was to elucidate the role of CDC20 in cancer cell invasiveness and to identify novel natural inhibitors of CDC20. The authors found that CDC20 knockdown inhibited the migration of chemoresistant PANC­1 pancreatic cancer cells and the metastatic MDA­MB­231 breast cancer cell line. By contrast, the overexpression of CDC20 by plasmid transfection promoted the metastasizing capacities of the PANC­1 cells and MCF­7 breast cancer cells. It was also identified that a triterpene mixture extracted from the mushroom Poria cocos (PTE), purified triterpenes dehydropachymic acid, and polyporenic acid C (PPAC) downregulated the expression of CDC20 in PANC­1 cells dose­dependently. Migration was also suppressed by PTE and PPAC in a dose­dependent manner, which was consistent with expectations. Taken together, the present study is the first, to the best of our knowledge, to demonstrate that CDC20 serves an important role in cancer metastasis and that triterpenes from P. cocos inhibit the migration of pancreatic cancer cells associated with CDC20. Further investigations are in progress to investigate the specific mechanism associated with CDC20 and these triterpenes, which may have future potential use as natural agents in the treatment of metastatic cancer.