2. Academic Validation
  3. The therapeutic value of SC66 in human renal cell carcinoma cells

The therapeutic value of SC66 in human renal cell carcinoma cells

  • Cell Death Dis. 2020 May 11;11(5):353. doi: 10.1038/s41419-020-2566-1.
Ming Xu  # 1,  Yin Wang  # 2,  Li-Na Zhou  # 3,  Li-Jun Xu  # 1,  Zhi-Chang Jin 4,  Dong-Rong Yang 5,  Min-Bin Chen 6,  Jin Zhu 7
Affiliations

Affiliations

  • 1 Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • 2 Institute of Neuroscience, Soochow University, Suzhou, China.
  • 3 Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China.
  • 4 Department of Urology, Ningbo Urology Nephrology Hospital, Ningbo, China.
  • 5 Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China. doc_ydr@163.com.
  • 6 Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China. cmb1981@163.com.
  • 7 Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China. urologistzhujin@163.com.
  • # Contributed equally.
PMID: 32393791 DOI: 10.1038/s41419-020-2566-1
Abstract

The PI3K-AKT-mTOR cascade is required for renal cell carcinoma (RCC) progression. SC66 is novel Akt Inhibitor. We found that SC66 inhibited viability, proliferation, migration and invasion of RCC cell lines (786-O and A498) and patient-derived primary RCC cells. Although SC66blocked AKT-mTORC1/2 activation in RCC cells, it remained cytotoxic in AKT-inhibited/-silenced RCC cells. In RCC cells, SC66 cytotoxicity appears to occur via Reactive Oxygen Species (ROS) production, sphingosine kinase 1inhibition, ceramide accumulation and JNK activation, independent of Akt inhibition. The ROS scavenger N-acetylcysteine, the JNK Inhibitor (JNKi) and the anti-ceramide sphingolipid sphingosine-1-phosphate all attenuated SC66-induced cytotoxicity in 786-O cells. In vivo, oral administration of SC66 potently inhibited subcutaneous 786-O xenograft growth in SCID mice. AKT-mTOR inhibition, SphK1 inhibition, ceramide accumulation and JNK activation were detected in SC66-treated 786-O xenograft tumors, indicating that SC66 inhibits RCC cell progression through AKT-dependent and AKT-independent mechanisms.

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