Different Role of Raptor and Rictor in Regulating Rasfonin‐Induced Autophagy and Apoptosis in Renal Carcinoma Cells

• Published in: Chemistry & biodiversity 2020-12, Vol.17 (12), p.e2000743-n/a
• Main Authors: Hou, Bolin, Liu, Shuchun, Li, Erwei, Jiang, Xuejun
• Format: Article
• Language: English
• Subjects: AKT protein; Apoptosis; Autophagy; Caspase; Kidney cancer; Natural products; Phagocytosis; Poly(ADP-ribose) polymerase; Rapamycin; Raptor; rasfonin; Renal cell carcinoma; Rictor; TOR protein
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.202000743

Both Raptor and Rictor are the key components in the complexes of mammalian target of rapamycin (mTOR), which play a vital role in mediating autophagy. Unlike mTOR, the regulatory role of either Raptor or Rictor in the regulation of autophagic process is relatively less explored. In present study, we found that rasfonin, which isolated from Talaromyces sp. 3656‐A1 and was a fungal natural product, activated both caspase‐dependent apoptosis and autophagy in ACHN, a renal carcinoma cell line. Knockdown of Raptor decreased both rasfonin‐induced autophagic flux and PARP‐1 cleavage, and in contrast, Rictor silencing increased apoptosis concomitantly enhancing rasfonin‐induced autophagy. Unexpectedly, API‐2, which was widely used as an inhibitor of Akt, promoted rasfonin‐dependent autophagy in Raptor‐depleted but not Rictor‐deprived cells. Collectively, these results demonstrated that Raptor and Rictor could play a distinctly regulatory role in rasfonin‐enhanced autophagy and apoptosis.