Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells

Kim,Dahee; Koh,Byumseok; Kim,Kwang  Rok; Kim,Ki  Young; Jung,Won  Hoon; Kim,Hi  Youn; Kim,Sungsub; Rhee,Sang  Dal

doi:10.3892/ol.2019.10813

Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3‑dimensional culture of colorectal cancer cells

Authors:
- Dahee Kim
- Byumseok Koh
- Kwang Rok Kim
- Ki Young Kim
- Won Hoon Jung
- Hi Youn Kim
- Sungsub Kim
- Sang Dal Rhee
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Affiliations: Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, Yuseong‑gu, Daejeon 34114, Republic of Korea, Graduate School of New Drug Discovery and Development, Chungnam National University, Yuseong‑gu, Daejeon 34134, Republic of Korea
Published online on: September 5, 2019 https://doi.org/10.3892/ol.2019.10813
Pages: 4858-4864
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

XAV939, a tankyrase inhibitor, exerts an anticancer effect in 3‑dimensional (3D) cultured SW480 cells, however this is not exhibited in 2‑dimensional (2D) cultured SW480 cells. In the current study, XAV939 induced a 3.7‑fold increase in cellular apoptosis in 3D culture but not in the 2D culture. However, no significant changes were indicated in cell cycle distribution in the 2D or 3D culture. Based on the observation that protein expression, which was associated with the glycolytic pathway, was increased in the 3D culture, the effect of XAV939 on the patterns of glycolytic protein expression was assessed. XAV939 was revealed to decrease lactose dehydrogenase A (LDHA) expression in 3D cultured SW480 cells, but only exerted a small effect in the 2D culture. The coadministration of XAV939 with the LDHA inhibitor FX11 decreased proliferation in 3D cultured SW480 cells compared with the single administration of FX11, while there was no additive effect in the 2D culture. The lactate assay also indicated that XAV939 decreased lactate secretion in the 3D cell culture but not in the 2D culture. These results suggest that XAV939 exerts an anticancer effect through inhibition of LDHA in the 3D culture.

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