Open Access

Dihydroartemisinin inhibits ATP6 activity, reduces energy metabolism of hepatocellular carcinoma cells, promotes apoptosis and inhibits metastasis via CANX

  • Authors:
    • Jiang Chang
    • Qingzhuang Yang
    • Xiangwei Liu
    • Wang Li
    • Lianghui Gao
  • View Affiliations

  • Published online on: August 2, 2024     https://doi.org/10.3892/ol.2024.14607
  • Article Number: 474
  • Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dihydroartemisinin (DHA) may inhibit the migration and invasion of liver cancer cells by reducing ATP synthase production (specifically ATP1A1 and ATP5H) through the calcium/calmodulin dependent protein kinase kinase 2/solute carrier family 8 member B1 signaling pathway. However, it is unclear whether DHA regulates ATP synthase activity by modulating other calcium ion signals to inhibit the energy metabolism and the transfer of hepatocellular carcinoma (HCC) cells. Using the Gene Expression Profiling Interactive Analysis database, a search for specific expression genes in liver cancer tissues was performed. Human HCC HuH‑7 and Li‑7 cells were used to produce CANX overexpression and small interfering RNA cell models. The study assessed changes in cell proliferation, apoptosis, migration and invasion. Reactive oxygen species production, ATP production, mitochondrial membrane potential (JC‑1), NAD+/NADH ratio and mitochondrial fluorescence were also evaluated. Western blotting was used to assess changes in CANX, ATP6V1 domain (ATP6V1F) and V0 domain (ATP6V0B) protein expression levels. The results demonstrated that CANX is highly expressed in liver cancer tissues. Furthermore, CANX regulated malignant biological behavior, mediated mitochondrial function and energy metabolism. However, these effects were inhibited by DHA, which decreased the expression of CANX, ATP6V0B and ATP6V1F. The findings of the present study underscore the central role of CANX in affecting the malignant biological behavior of liver cancer cells by regulating mitochondrial function and energy metabolism. Additionally, they indicate that DHA serves an anticancer role by inhibiting CANX expression.
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October-2024
Volume 28 Issue 4

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Spandidos Publications style
Chang J, Yang Q, Liu X, Li W and Gao L: Dihydroartemisinin inhibits ATP6 activity, reduces energy metabolism of hepatocellular carcinoma cells, promotes apoptosis and inhibits metastasis via CANX. Oncol Lett 28: 474, 2024.
APA
Chang, J., Yang, Q., Liu, X., Li, W., & Gao, L. (2024). Dihydroartemisinin inhibits ATP6 activity, reduces energy metabolism of hepatocellular carcinoma cells, promotes apoptosis and inhibits metastasis via CANX. Oncology Letters, 28, 474. https://doi.org/10.3892/ol.2024.14607
MLA
Chang, J., Yang, Q., Liu, X., Li, W., Gao, L."Dihydroartemisinin inhibits ATP6 activity, reduces energy metabolism of hepatocellular carcinoma cells, promotes apoptosis and inhibits metastasis via CANX". Oncology Letters 28.4 (2024): 474.
Chicago
Chang, J., Yang, Q., Liu, X., Li, W., Gao, L."Dihydroartemisinin inhibits ATP6 activity, reduces energy metabolism of hepatocellular carcinoma cells, promotes apoptosis and inhibits metastasis via CANX". Oncology Letters 28, no. 4 (2024): 474. https://doi.org/10.3892/ol.2024.14607