Dauricine inhibits viability and induces cell cycle arrest and apoptosis via inhibiting the PI3K/Akt signaling pathway in renal cell carcinoma cells

Mol Med Rep. 2018 May;17(5):7403-7408. doi: 10.3892/mmr.2018.8732. Epub 2018 Mar 14.

Abstract

Renal cell carcinoma (RCC), which is derived from the proximal tubules of nephrons, is one of the most common solid cancers. Due to its inherent insensitivity to radiotherapy and chemotherapy, surgery remains the only curative strategy for RCC. Therefore, a novel strategy for treating RCC is urgently needed. This study aims to investigate the effects of dauricine, a bisbenzylisoquinoline alkaloid, in RCC cells and the underlying mechanisms of its action. The effects of dauricine on viability, cell cycle distribution and apoptosis in RCC cells were determined in vitro by MTT assay, flow cytometry and nucleosome ELISA assay, respectively. Mechanism studies were performed by analyzing related proteins using western blotting assays. We show that dauricine effectively inhibits the viability of four RCC cell lines (786‑O, Caki‑1, A‑498 and ACHN). In addition, dauricine induces cell cycle arrest at the G0/G1 phase in RCC cells. Dauricine also induces apoptosis via the intrinsic pathway, since caspase‑9 and caspase‑3 but not caspase‑8 activation was detected after the treatment. Moreover, dauricine was able to inhibit the PI3K/Akt signaling pathway. Our findings suggest inhibitory effects of dauricine in renal cancer cells and provide a better understanding of its underlying mechanism. Our findings suggest that dauricine could be a potential therapeutic agent for treating RCC.

Keywords: renal cell carcinoma; dauricine; apoptosis; cell cycle; PI3K/Akt.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzylisoquinolines / pharmacology*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects*
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Tetrahydroisoquinolines / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzylisoquinolines
  • Tetrahydroisoquinolines
  • dauricine
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt