Artemisia annua L. Polyphenols Enhance the Anticancer Effect of β-Lapachone in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cellsopen access
- Authors
- Jung, Eun Joo; Kim, Hye Jung; Shin, Sung Chul; Kim, Gon Sup; Jung, Jin-Myung; Hong, Soon Chan; Kim, Choong Won; Lee, Won Sup
- Issue Date
- Dec-2023
- Publisher
- Multidisciplinary Digital Publishing Institute (MDPI)
- Keywords
- anticancer effect; Artemisia annua L. polyphenols; chemotherapy; colorectal cancer; oxaliplatin-resistant; phytochemical; β-lapachone
- Citation
- International Journal of Molecular Sciences, v.24, no.24
- Indexed
- SCIE
SCOPUS
- Journal Title
- International Journal of Molecular Sciences
- Volume
- 24
- Number
- 24
- URI
- https://scholarworks.gnu.ac.kr/handle/sw.gnu/69197
- DOI
- 10.3390/ijms242417505
- ISSN
- 1661-6596
1422-0067
- Abstract
- Recent studies suggest that the anticancer activity of β-lapachone (β-Lap) could be improved by different types of bioactive phytochemicals. The aim of this study was to elucidate how the anticancer effect of β-Lap is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in parental HCT116 and oxaliplatin-resistant (OxPt-R) HCT116 colorectal cancer cells. Here, we show that the anticancer effect of β-Lap is more enhanced by pKAL in HCT116-OxPt-R cells than in HCT116 cells via a CCK-8 assay, Western blot, and phase-contrast microscopy analysis of hematoxylin-stained cells. This phenomenon was associated with the suppression of OxPt-R-related upregulated proteins including p53 and β-catenin, the downregulation of cell survival proteins including TERT, CD44, and EGFR, and the upregulation of cleaved HSP90, γ-H2AX, and LC3B-I/II. A bioinformatics analysis of 21 proteins regulated by combined treatment of pKAL and β-Lap in HCT116-OxPt-R cells showed that the enhanced anticancer effect of β-Lap by pKAL was related to the inhibition of negative regulation of apoptotic process and the induction of DNA damage through TERT, CD44, and EGFR-mediated multiple signaling networks. Our results suggest that the combination of pKAL and β-Lap could be used as a new therapy with low toxicity to overcome the OxPt-R that occurred in various OxPt-containing cancer treatments. © 2023 by the authors.
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