Cordycepol C Induces Caspase-Independent Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells

Abstract

Cordycepol C, a novel sesquiterpene isolated from the cultured mycelia of Cordyceps ophioglossoides, contains a hydroperoxy group and is cytotoxic to HepG2 cells. So far, no sesquiterpenes have been found in the genus Cordyceps and it would be interesting to investigate the antitumor efficacy as well as the mechanism of action of this unusual sesquiterpene. In this study, we showed that cordycepol C induced apoptosis of the HepG2 cells without affecting the normal liver cell line L-02. Cordycepol C caused poly(ADP-ribose) polymerase-1 (PARP-1) cleavage and triggered the loss of mitochondrial membrane potential (Δψ m ) in HepG2 cells in a time-and dose-dependent manner, resulting in the nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease G (Endo G). We also found that cordycepol C induced the expression of Bax protein, followed by its translocation from the cytosol to mitochondria in both wild type and p53 knockdown HepG2 cells. However, cordycepol C could not cause cleavages of procaspase-3, -8, and -9. Caspase activities were not increased and Z-VAD-fmk, a caspase inhibitor, could not prevent the apoptosis induced by cordycepol C. These findings indicate that cordycepol C induces caspase-independent apoptosis in HepG2 cells through a p53-independent and Bax-mediated mitochondrial pathway, leading to the nuclear translocation of AIF and Endo G. Our study provides the molecular mechanism by which cordycepol C induces apoptosis in hepatocellular carcinoma cells and indicates the potential use of cordycepol C as an antitumor agent.

Brazilian green propolis induced apoptosis in human lung cancer A549 cells through mitochondrial-mediated pathway

“…Interestingly, we observed that the expression of gene Caspase‐3 not was changed; however, the ΔΨm was disrupted by our sample in A549 cells. Several studies revealed that mitochondria contain different apoptogenic factors, including apoptosis‐inducing factor (AIF) and endonuclease G (EndoG), which have crucial roles in caspase‐independent apoptosis [45–47]. In fact, it has been reported that Bax‐induced cell death may not require caspase activity [48].…”

“…Several studies revealed that mitochondria contain different apoptogenic factors, including apoptosisinducing factor (AIF) and endonuclease G (EndoG), which have crucial roles in caspase-independent apoptosis. [45][46][47] In fact, it has been reported that Bax-induced cell death may not require caspase activity. [48] Our results suggest that Brazilian propolis or some of its bioactive constituents could induce Caspase-independent apoptosis by two different routes.…”

Identification of a mitochondrial‐targeting secretory protein from Nocardia seriolae which induces apoptosis in fathead minnow cells

“…The ΔΨm values were assessed at 24, 48 and 72 h.p.t. using the JC‐1 assay kit (Beyotime) by the method described previously with minor modification (Sun et al, ). The positive control was treated with carbonyl cyanide 3‐chlorophenylhydrazone (CCCP, 10 mM) to medium at 1:1,000 25°C for 20 min.…”

Identification and functional characterization of Histone‐like DNA‐binding protein in Nocardia seriolae (NsHLP) involved in cell apoptosis

“…Three pro‐apoptotic genes (Bcl‐2 antagonist of cell death ( Bad ), Bcl‐2 interacting domain death agonist ( Bid ) and Bcl‐2 associated X protein ( Bax )) were chosen, and their mRNA expression levels were measured using a previously described method with minor modifications (Sun et al, ). Three groups of transfected FHM cells were harvested at 0, 24, 48, 72 and 96 hpt to extract the total RNA, and quantitative real‐time PCR (qRT–PCR) was conducted following cDNA synthesis.…”