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Cultivated and wild Pleurotus ferulae ethanol extracts inhibit hepatocellular carcinoma cell growth via inducing endoplasmic reticulum stress- and mitochondria-dependent apoptosis.

ABSTRACT: Pleurotus ferulae is a kind of editable mushroom and has various biological functions such as antitumor, antioxidation and immunoregulation. Wild P. ferulae was successfully domesticated but the antitumor function and mechanisms of cultivated and wild P. ferulae need to be compared and explored. Here, we prepared cultivated and wild P. ferulae ethanol extracts (PFEE-C and PFEE-W) and compared their antitumor effect on hepatocellular carcinoma. Our data showed that PFEE-C and PFEE-W significantly inhibited the growth of H22 and HepG2 cells through induction of apoptosis. PFEE-W exhibited higher antitumor activity than PFEE-C. Both PFEE-C and PFEE-W induced endoplasmic reticulum (ER) stress characterized by the up-regulated levels of phosphorylated JNK, cleaved caspase-12 and HSP70, and mitochondrial dysfunction characterized by the reduction of mitochondrial membrane potential and the release of cytochrome c, which promoted the cleavage of caspase-3, -7, -9 and PARP. Moreover, PFEE-C and PFEE-W significantly increased ROS generation in H22 cells and suppressed H22 cell migration through reducing the levels of matrix metalloproteinase -2 and -9. Further, PFEE-C inhibited H22 tumor growth in mouse model and improved the survival of tumor mice. These results indicated that PFEE-C and PFEE-W could inhibit hepatocellular carcinoma cell growth through ER stress- and mitochondria-dependent apoptotic pathways.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6143524 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Cultivated and wild Pleurotus ferulae ethanol extracts inhibit hepatocellular carcinoma cell growth via inducing endoplasmic reticulum stress- and mitochondria-dependent apoptosis.

Yang Yi Y Yuan Pengfei P Wei Xianxian X Fu Changshuang C Li Jinyu J Wang Weilan W Wang Xinhui X Li Yijie Y Li Jinyao J

Scientific reports 20180918 1

Pleurotus ferulae is a kind of editable mushroom and has various biological functions such as antitumor, antioxidation and immunoregulation. Wild P. ferulae was successfully domesticated but the antitumor function and mechanisms of cultivated and wild P. ferulae need to be compared and explored. Here, we prepared cultivated and wild P. ferulae ethanol extracts (PFEE-C and PFEE-W) and compared their antitumor effect on hepatocellular carcinoma. Our data showed that PFEE-C and PFEE-W significantly ...[more]

PMID: 30228276

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Project description:BackgroundUseful probes of the intracellular environment that target a specific organelle in order to allow direct observation of the changes in these regions is of high current interest. Macrocyclic ligands have already revealed themselves as important selective hosts in some biological applications, forming stable and specific complexes. Therefore, in this paper, several macrocyclic ligands are evaluated as potential molecular probes.MethodologyFour polyammonium macrocycles and one macrotricyclic bearing pyridine and phenanthroline chromophores have been synthesised and evaluated as molecular probes. The cytotoxicity of the compounds has been analyzed using human breast cancer cells (MCF-7), non-cancerous human dermal fibroblasts (NHDF) and human adult dermal skin fibroblasts from a breast cancer patient (P14). All the compounds showed low toxicity at concentrations ranging from 10 nM to 10 µM, except for [32]phen(2)N(4) which proved to be highly cytotoxic for MCF-7 cells. Flow cytometry studies evidenced that the percentage of apoptotic and necrotic MCF-7 and NHDF cells induced by the compounds is considerably low. Also, flow cytometry analysis showed that some compounds seem to modify the mitochondrial membrane potential (MMP) of the cells. Fluorescence microscopy evidenced that compounds easily cross the plasma membrane (5 min) and accumulated into the mitochondria, as confirmed by co-localization with MitoTracker Green™. The fluorescence images also evidenced an intact mitochondria structure after 48 h. Moreover, reticular staining suggestive of endoplasmic reticulum (ER) localization, in addition to the mitochondrial one, has been found by confocal microscopy.ConclusionOur study reveals that compounds Me(2)[28]py(2)N(6), cryptphen, [16]phenN(2), [30]phen(2)N(6), have low toxicity and localize in mitochondria and ER. The ability of these compounds for translocating the cellular membrane (5 min) without special conditioning of the cells or derivatization of the probe, the time-dependent localization (48 h) and the cellular viability provide a proof-of-concept towards their use as promising probes towards biomedical studies.

Dataset Information

Cultivated and wild Pleurotus ferulae ethanol extracts inhibit hepatocellular carcinoma cell growth via inducing endoplasmic reticulum stress- and mitochondria-dependent apoptosis.

Publications

Cultivated and wild Pleurotus ferulae ethanol extracts inhibit hepatocellular carcinoma cell growth via inducing endoplasmic reticulum stress- and mitochondria-dependent apoptosis.

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