Chronic exposure to the gibberellin derivative GA‑13315 sensitizes breast cancer MCF‑7 cells but not colon cancer HCT116 cells to irinotecan
- Xianliang Cheng
- Guohui Wang
- Yuan Liao
- Jiao Mo
- Chen Qing
Affiliations: School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, P.R. China
- Published online on: September 23, 2020 https://doi.org/10.3892/ol.2020.12144
Copyright: © Cheng
et al. This is an open access article distributed under the
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13‑Chlorine‑3,15‑dioxy‑gibberellic acid methyl ester (GA‑13315) is a gibberellin derivative that exhibits selective cytotoxicity to multidrug resistant MCF‑7/ADR cells and reverses drug resistance when administered at subtoxic doses in combination with chemotherapy drugs. The present study aimed to investigate the impact of chronic GA‑13315 exposure on the chemosensitivity of MCF‑7 and HCT116 cell lines. Cells were administered a subtoxic dose of 1 µM GA‑13315 for 12 weeks and the sensitivity of the cells to GA‑13315, irinotecan and cisplatin, was assessed. The Cell Counting Kit‑8 assay results demonstrated that the chronic exposure did not induce resistance to GA‑13315, in either MCF‑7 or HCT116 cells. Notably, MCF‑7 cells were sensitized to irinotecan following exposure to GA‑13315; however, HCT116 cells were not. The sensitizing effect of GA‑13315 was associated with the alterations of topoisomerase 1 (Top1) protein expression, tyrosyl DNA phosphodiesterase 1 and checkpoint kinase 1. Further analysis indicated that GA‑13315 caused DNA fragmentation; however, DNA damage was not mediated by a Top1‑dependent molecular mechanism, as GA‑13315 was revealed not to be a Top1 poison, despite inhibiting the catalytic activity of Top1. Taken together, the results of the present study indicated that GA‑13315 may be used for sensitizing MCF‑7 cells to irinotecan, as the chronic exposure of GA‑13315 to MCF‑7 cells still showed sensitizing effects to irinotecan.