The Cytotoxic and Mechanistic Effects of Aaptamine on Hepatocellular Carcinoma

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 16, 12 Issues, 2016

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex

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The Cytotoxic and Mechanistic Effects of Aaptamine on Hepatocellular Carcinoma

Anti-Cancer Agents in Medicinal Chemistry, 15(3): 291-297.

Author(s): Qiao-lu Li, Ping-ping Zhang, Pei-qin Wang, Hao-bing Yu, Fan Sun, Wen-zheng Hu, Wen-hui Wu, Xin Zhang, Fei Chen, Zhi-yong Chu, Jun-ping Zhang, Shun-shen Chen and Hou-wen Lin.

Affiliation: Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 PuJian Road, Pudong District, Shanghai 200127, China.


Hepatocellular carcinoma (HCC) is the fifth most common form of cancer and the third most frequent cause of cancer-associated mortality worldwide. We isolated aaptamine from the marine sponge Aaptos, and synthesized derivatives of this compound. Aaptamine and synthetic derivatives displayed various biological activities. This represents the first account of studies on the effects of aaptamine and its derivatives in hepatocarcinogenesis. In this study, Cell Counting Kit (CCK8) was used to evaluate the anti-proliferative effect of aaptamine on HCC in vitro. Additionally, a subcutaneous xenograft model was used to determine if aaptamine could inhibit hepatocellular carcinoma in vivo. We also used RT-PCR and Western blot to analyze the mechanisms behind these effects. Our results showed that aaptamine has anti-proliferation effects on the cell lines LM3 and HepG2. Aaptamine also suppressed the colony-formation ability of HCC cells. We found that aaptamine treatment led to cell cycle arrest in HCC cells, reduced the expression of SOX9 and CDK2. Significant anti-tumor effects were observed in aaptamineadministered tumor-bearing mice as compared to controls. However, structural changes made to aaptamine yielded two derivatives for which all the effects listed above were considerably reduced as compared to the original compound aaptamine. In conclusion, aaptamine is demonstrated for the first time to inhibit liver cancer progression. The aaptamine-induced cell cycle arrest was associated with the increased binding of p21 to Cdk2-cyclin D/E complexes, inhibition of Cdk2 kinase activity in HCC cells. Furthermore, aaptamine appears to be a promising and efficient treatment of liver cancer HCC-LM3 in vivo. We have also uncovered structural changes that might affect the biological activity. The work provides a promising drug candidate for HCC treatment.


Aaptamine, CDK2, hepatocellular carcinoma, SOX9.

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Article Details

Volume: 15
Issue Number: 3
First Page: 291
Last Page: 297
Page Count: 7
DOI: 10.2174/1871520614666141114201027
Price: $58

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