Flexicaulin A, an ent-kaurane diterpenoid, activates p21 and inhibits the proliferation of colorectal carcinoma cells through a non-apoptotic mechanism

Yixuan Xia, Chu Shing Lam, Wanfei Li, Md Shahid Sarwar, Kanglun Liu, Kwan Ming Lee, Hongjie ZHANG*, Siu Wai TSANG

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
1 Downloads (Pure)

Abstract

Natural products, explicitly medicinal plants, are an important source of inspiration of antitumor drugs, because they contain astounding amounts of small molecules that possess diversifying chemical entities. For instance, Isodon (formerly Rabdosia), a genus of the Lamiaceae (formerly Labiatae) family, has been reported as a rich source of natural diterpenes. In the current study, we evaluated the in vitro anti-proliferative property of flexicaulin A (FA), an Isodon diterpenoid with an ent-kaurane structure, in human carcinoma cells, by means of cell viability assay, flow cytometric assessment, quantitative polymerase chain reaction array, Western blotting analysis, and staining experiments. Subsequently, we validated the in vivo antitumor efficacy of FA in a xenograft mouse model of colorectal carcinoma. From our experimental results, FA appears to be a potent antitumor molecule, since it significantly attenuated the proliferation of human colorectal carcinoma cells in vitro and restricted the growth of corresponsive xenograft tumors in vivo without causing any adverse effects. Regarding its molecular mechanism, FA considerably elevated the expression level of p21 and induced cell cycle arrest in the human colorectal carcinoma cells. While executing a non-apoptotic mechanism, we believe the antitumor potential of FA opens up new horizons for the therapy of colorectal malignancy.

Original languageEnglish
Article number1917
JournalInternational Journal of Molecular Sciences
Volume20
Issue number8
DOIs
Publication statusPublished - 2 Apr 2019

Scopus Subject Areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

User-Defined Keywords

  • Cell cycle arrest
  • Colorectal carcinoma
  • Diterpenoid
  • Ent-kaurane
  • P21

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