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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01287

In vitro and in vivo antitumor activity of cucurbitacin C, a novel natural product from cucumber

 Dinglan Wu1,  Zhu Wang2,  Muqi Lin3, Yi Shang4, Fei Wang5,  Fei Wang6, Jiayi Zhou7,  Xiaomin Luo6 and Weiren Huang8*
  • 1Shenzhen Hospital, Southern Medical University, China
  • 2Department of Urology, People's Hospital of Longhua, Shenzhen, China
  • 3Health Science Center, Shenzhen University, China
  • 4Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, China
  • 5Department of Urology, Hainan General Hospital, China
  • 6Peking University Shenzhen Hospital, China
  • 7Peking University Shenzhen Hospital, China
  • 8Department of Urology, Shenzhen Second People’s Hospital, China

Cucurbitacin C (CuC), a novel analogue of triterpenoids cucurbitacins, confers a bitter taste in cucumber. Genes and signaling pathways responsive for biosynthesis of CuC have been identified in the recent years. In the present study, we explored the anti-cancer effects of CuC against human cancers in vitro and in vivo. CuC inhibited proliferation and clonogenic potential of multiple cancer cells in a dose dependent manner. Low dose CuC treatment induced cell cycle arrest at G1 or G2/M stage in different cancer lines, whereas high dose treatment of CuC caused apoptosis in cancer cells. PI3K-Akt signaling pathway was found to be one of the major pathways involved in CuC-induced cell growth arrest and apoptosis by RNA-Seq and western blotting. Mechanistic dissection further confirmed that CuC effectively inhibited the Akt signaling by inhibition of Akt phosphorylation at Ser473. In vivo CuC treatment (0.1 mg/kg body weight) effectively inhibited growth of cancer cells derived xenograft tumors in athymic nude mice and caused significant apoptosis. Our findings for the first time demonstrated the potential therapeutic significance of CuC against human cancers.

Keywords: cucurbitacin C, natural product, anti-cancer, AKT pathway, Growth arrest, Apoptosis

Received: 13 May 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Wu, Wang, Lin, Shang, Wang, Wang, Zhou, Luo and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Weiren Huang, Department of Urology, Shenzhen Second People’s Hospital, Shenzhen, China, pony8980@163.com