Antineoplastic activity of cucurbitacin I in CC531 rat colorectal cancer cells

Author Info

E. Eyol E. Tosun F Karaku? H. Adwan K. Y?lmaz M Kovacheva M. Zepp Martin R. Berger

Corresponding Author

Martin R. Berger
Chemotherapy and Toxicology Unit, German Cancer Research Center, Heidelberg, Germany

A B S T R A C T

Purpose: The triterpenoid Cucurbitacin I (Cu I; isolated from Iberis amara), which is a natural inhibitor of JAK/STAT3 was examined for its antineoplastic effect in CC531 rat colon cancer cells in vitro and in vivo. Methods: Initially, the antiproliferative effect of Cu I was studied by MTT assay and anti-migratory effects by wound healing assay. Then, a colony assay was used to determine the inhibition of colony formation in response to Cu I. Cell cycle changes were analyzed by propidium iodide staining and apoptosis induction was evaluated by annexin V staining, using flow cytometry, respectively. Hoechst 33342 staining was utilized to detect changes in nuclear morphology. Detection of Stat3 and pStat3 proteins was done by Western blot. The orthotopic CC531 model for colorectal cancer liver metastasis was instrumental for assessing the antitumor effect of Cu I in vivo. Results: Our results show that Cu I can inhibit the proliferation and migration of CC531 cells in a doseand time-dependent manner. Colony formation was completely suppressed at concentrations corresponding to one third of the IC50. Furthermore, exposure to Cu I resulted in accumulation of G1/M phase- and apoptotic cells in vitro. Stat3 was detected in CC531 cells growing in vitro, but pStat3 was noticed only in vivo. Treatment with maximum tolerated doses of Cu I (200 - 300 µg/kg) did not result into significant inhibition of colorectal liver metastases in vivo. Conclusions: These findings demonstrate that the measurable antineoplastic activity of Cu I does not depend on the presence of pStat3.

Article Info

Article Type

Research Article

Publication history

Received: Sat 09, Feb 2019
Accepted: Fri 01, Mar 2019
Published: Mon 11, Mar 2019

Copyright

© 2023 Martin R. Berger. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.COR.2019.01.105