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CDC20 associated with cancer metastasis and novel mushroom‑derived CDC20 inhibitors with antimetastatic activity
Shujie Cheng1, Victor Castillo2, Daniel Sliva2
1Department of Food Quality and Safety, School of Engineering, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China.
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 PANC‑1 pancreatic cancer cells and the metastatic MDA‑MB‑231 breast cancer cell line. By contrast, the overexpression of CDC20 by plasmid transfection promoted the metastasizing capacities of the PANC‑1 cells and MCF‑7 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 PANC‑1 cells dose‑dependently. Migration was also suppressed by PTE and PPAC in a dose‑dependent 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.
Insights
Cell division cycle 20 (CDC20) drives cancer metastasis. Natural compounds from Poria cocos, like PTE and PPAC, inhibit CDC20 expression and reduce pancreatic cancer cell migration.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Aberrant cell division cycle 20 (CDC20) expression correlates with cancer progression and poor prognosis.
- Targeting CDC20 presents a potential therapeutic strategy for cancers with elevated CDC20 levels.
Purpose of the Study:
- To investigate the role of CDC20 in cancer cell invasiveness.
- To identify natural compounds that inhibit CDC20 and cancer cell migration.
Main Methods:
- CDC20 gene knockdown and overexpression in pancreatic (PANC-1) and breast (MDA-MB-231, MCF-7) cancer cell lines.
- Treatment of PANC-1 cells with triterpene mixture (PTE) and purified triterpenes (dehydropachymic acid, polyporenic acid C - PPAC) from Poria cocos.
- Assessment of cell migration and CDC20 expression levels.
Main Results:
- CDC20 knockdown inhibited migration in PANC-1 and MDA-MB-231 cells.
- CDC20 overexpression promoted metastasis in PANC-1 and MCF-7 cells.
- PTE and PPAC dose-dependently downregulated CDC20 expression and suppressed migration in PANC-1 cells.
Conclusions:
- CDC20 plays a significant role in cancer metastasis.
- Triterpenes from Poria cocos inhibit pancreatic cancer cell migration by downregulating CDC20.
- These natural compounds show potential as therapeutic agents for metastatic cancer.
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