Journal
FRONTIERS IN PHARMACOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2019.01287
Keywords
cucurbitacin C; natural product; anti-cancer; growth arrest; apoptosis; Akt pathway
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Funding
- Science and Technology Project of Shenzhen [JCYJ20170307144115825, JCYJ2018 0508163203807]
- Shenzhen Key Laboratory of Viral Oncology [ZDSYS201707311140430]
- National Natural Science Foundation of China [81772737, 81502570]
- National Science Foundation Projects of Guangdong Province [2017B030301015]
- Sanming Project of Medicine in Shenzhen [SZSM201612023, SZSM201412018]
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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.
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