Fungal secondary metabolites rasfonin induces autophagy, apoptosis and necroptosis in renal cancer cell line

Abstract

Rasfonin (A304) is a fungal natural product isolated from the fermentation substrate of Talaromyces sp. 3656-A1, which was named according to its activity against the small G-protein Ras. In a former study, we demonstrated that it induced autophagy and apoptosis; however, whether rasfonin activated necroptosis remained unknown. Moreover, the interplay among different cell death processes induced by rasfonin was unexplored. In the present study, we revealed that, in addition of promoting autophagy and caspase-dependent apoptosis, rasfonin also activated necroptosis. Nectrostatin-1 (Nec-1), an inhibitor of necroptosis, affected rasfonin-induced autophagy in a time-dependent manner concurring with an increased caspase-dependent apoptosis. The aforementioned results were confirmed by knockdown of receptor-interacting protein 1 (RIP1), a crucial necrostatin-1-targeted adaptor kinase mediating cell death and survival. Taken together, the data presented indicate that rasfonin activates various cell death pathways, and RIP1 plays a critical role in rasfonin-induced autophagy and apoptosis.

Autophagy as a Vital Therapy Target for Renal Cell Carcinoma

“…In ACHN cell lines, sinomenine, an isoquinoline extracted from Sinomenium acutum , inhibited RCC progression by inducing autophagy via Beclin1 and LC3-Ⅱ/LC3-Ⅰ up-regulation and p62 down-regulation (F. Deng et al, 2018 ). Rasfonin (A304), a product of Talaromyces sp , activates the death of RCC cells by inducing autophagy, and this effect could be suppressed by the Akt inhibitor ( Lu et al, 2015 ; Sun et al, 2016 ).…”

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

“…In the previous study, we have revealed that rasfonin can promote autophagic flux and activate various cell death pathways. [28] Our present data demonstrated that knockdown of Rictor enhanced rasfonin-activated autophagy and caspase-dependent apoptosis, [29] whereas deprivation of raptor decreased both rasfonin-induced autophagic flux and PARP-1 cleavage. Interestingly, chemical inhibition of Akt appeared to differentially affect rasfonin-induced autophagic process in either Raptor-or Rictor-depleted cells.…”

Production of Terretonin N and Butyrolactone I by Thermophilic Aspergillus terreus TM8 Promoted Apoptosis and Cell Death in Human Prostate and Ovarian Cancer Cells

“…Research has been focused on the potential, valuable biological activity of terrestrial fungal metabolites, particularly cancer therapeutics [ 18 , 19 ]. The characterized fungal metabolites in this study surprisingly displayed remarkable antitumor properties via the induction of cellular apoptosis in both human metastatic prostate cells (PC-3) and ovarian adenocarcinoma cells (SKOV3) lines.…”

“…The characterized fungal metabolites in this study surprisingly displayed remarkable antitumor properties via the induction of cellular apoptosis in both human metastatic prostate cells (PC-3) and ovarian adenocarcinoma cells (SKOV3) lines. Previously, some metabolites isolated from different fungi or lichens have progressed into anticancer activity [ 18 , 19 , 20 ], where anticancer activities displayed more potent cytotoxicity with more cellular apoptosis [ 18 , 19 , 20 ].…”

“…Conversely, other fungal metabolites activate various cell death pathways, apoptosis, autophagic cell death, and programmed necrosis (necroptosis) [ 23 , 24 ]. In a recent study, rasfonin (A304) isolated from Talaromyces sp ., promoted autophagy and caspase-dependent apoptosis in cancer cells [ 19 ].…”