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

Dinglan Wu; Zhu Wang; Muqi Lin; Yi Shang; Fei Wang; JiaYi Zhou; Fei Wang; Xiantong Zhang; Xiaomin Luo; Weiren Huang

doi:10.3389/fphar.2019.01287

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. eCollection 2019.

Authors

Dinglan Wu¹, Zhu Wang², Muqi Lin³, Yi Shang⁴, Fei Wang⁵, JiaYi Zhou¹, Fei Wang¹, Xiantong Zhang¹, Xiaomin Luo¹, Weiren Huang⁶

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.