1. Academic Validation
  2. In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber

In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber

  • Front Pharmacol. 2019 Nov 8:10:1287. doi: 10.3389/fphar.2019.01287.
Dinglan Wu 1 Zhu Wang 2 Muqi Lin 3 Yi Shang 4 Fei Wang 5 JiaYi Zhou 1 Fei Wang 1 Xiantong Zhang 1 Xiaomin Luo 1 Weiren Huang 6
Affiliations

Affiliations

  • 1 Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
  • 2 Department of Urology, People's Hospital of Longhua Shenzhen, Southern Medical University, Shenzhen, China.
  • 3 School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.
  • 4 Agricultural Genome Institute at Shenzhen, Chinese Academy of Agricultural Science, Shenzhen, China.
  • 5 Department of Urology, The Hospital of Hainan Province, Haikou, China.
  • 6 Department of Urology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, International Cancer Center, Shenzhen University School of Medicine, Shenzhen, China.
Abstract

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 cell-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

Akt pathway; anti-cancer; apoptosis; cucurbitacin C; growth arrest; natural product.

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