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Fungal 7-epi-10-deacetyltaxol produced by an endophytic Pestalotiopsis microspora induces apoptosis in human hepatocellular carcinoma cell line (HepG2).

ABSTRACT: Paclitaxel (taxol) is a potent anticancer drug that is used in the treatment of a wide variety of cancerous. In the present study, we identified a taxol derivative named 7-epi-10-deacetyltaxol (EDT) from the culture of an endophytic fungus Pestalotiopsis microspora isolated from the bark of Taxodium mucronatum. This study was carried out to investigate the effects of fungal EDT on cell proliferation, the induction of apoptosis and the molecular mechanisms of apoptosis in human hepatoma HepG2 cells in vitro.The endophytic fungus was identified by traditional and molecular taxonomical characterization and the fungal EDT was purified using column chromatography and confirmed by various spectroscopic and chromatographic comparisons with authentic paclitaxel. We studied the in vitro effects of EDT on HepG2 cells for parameters such as cell cycle distribution, DNA fragmentation, reactive oxygen species (ROS) generation and nuclear morphology. Further, western blot analysis was used to evaluate Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), p38-mitogen activated protein kinase (MAPK) and poly [ADP-ribose] polymerase (PARP) expression.We demonstrate that the fungal EDT exhibited significant in vitro cytotoxicity in HepG2 cells. We investigated cytotoxicity mechanism of EDT in HepG2 cells. The results showed nuclear condensation and DNA fragmentation were observed in cells treated with fungal EDT. Besides, the fungal EDT arrested HepG2 cells at G2/M phase of cell cycle. Furthermore, fungal EDT induced apoptosis in HepG2 cells in a dose-dependent manner associated with ROS generation and increased Bax/Bcl-2 ratio, p38 MAPKs and PARP cleavage.Our data show that EDT induced apoptotic cell death in HepG2 cells occurs through intrinsic pathway by generation of ROS mediated and activation of MAPK pathway. This is the first report for 7-epi-10-deacetyltaxol (EDT) isolated from a microbial source.

SUBMITTER: Subban K

PROVIDER: S-EPMC5706334 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Fungal 7-epi-10-deacetyltaxol produced by an endophytic Pestalotiopsis microspora induces apoptosis in human hepatocellular carcinoma cell line (HepG2).

Subban Kamalraj K Singh Satpal S Subramani Ramesh R Johnpaul Muthumary M Chelliah Jayabaskaran J

BMC complementary and alternative medicine 20171128 1

<h4>Background</h4>Paclitaxel (taxol) is a potent anticancer drug that is used in the treatment of a wide variety of cancerous. In the present study, we identified a taxol derivative named 7-epi-10-deacetyltaxol (EDT) from the culture of an endophytic fungus Pestalotiopsis microspora isolated from the bark of Taxodium mucronatum. This study was carried out to investigate the effects of fungal EDT on cell proliferation, the induction of apoptosis and the molecular mechanisms of apoptosis in human ...[more]

PMID: 29183320

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Project description:An endophytic fungal strain isolated from the leaves of Gymnema sylvestre was identified as Pestalotiopsis microspora VJ1/VS1 based on nucleotide sequencing of internal transcribed spacer region (ITS 1-5.8S-ITS 2) of 18S rRNA gene (NCBI accession number KX213894). In this study, an efficient and ecofriendly approach has been reported for the synthesis of silver nanoparticles (AgNPs) using aqueous culture filtrate of P. microspora. Ultraviolet-visible analysis confirmed the synthesis of AgNPs by showing characteristic absorption peak at 435 nm. Fourier transform infrared spectroscopy analysis revealed the presence of phenolic compounds and proteins in the fungal filtrate, which are plausibly involved in the biosynthesis and capping of AgNPs. Transmission electron microscopy (TEM) showed that the AgNPs were spherical in shape of 2-10 nm in size. Selected area electron diffraction and X-ray diffraction studies determined the crystalline nature of AgNPs with face-centered cubic (FCC) lattice phase. Dynamic light scattering analysis showed that the biosynthesized AgNPs possess high negative zeta potential value of -35.7 mV. Biosynthesized AgNPs were proved to be potential antioxidants by showing effective radical scavenging activity against 2,2'-diphenyl-1-picrylhydrazyl and H2O2 radicals with IC50 values of 76.95±2.96 and 94.95±2.18 µg/mL, respectively. The biosynthesized AgNPs exhibited significant cytotoxic effects against B16F10 (mouse melanoma, IC50 =26.43±3.41 µg/mL), SKOV3 (human ovarian carcinoma, IC50 =16.24±2.48 µg/mL), A549 (human lung adenocarcinoma, IC50 =39.83±3.74 µg/mL), and PC3 (human prostate carcinoma, IC50 =27.71±2.89 µg/mL) cells. The biosynthesized AgNPs were found to be biocompatible toward normal cells (Chinese hamster ovary cell line, IC50 =438.53±4.2 µg/mL). Cytological observations on most susceptible SKOV3 cells revealed concentration-dependent apoptotic changes that include cell membrane blebbing, cell shrinkage, pyknotic nuclei, karyorrhexis followed by destructive fragmentation of nuclei. The results together in this study strongly provided a base for the development of potential and versatile biomedical applications of biosynthesized AgNPs in the near future.

Dataset Information

Fungal 7-epi-10-deacetyltaxol produced by an endophytic Pestalotiopsis microspora induces apoptosis in human hepatocellular carcinoma cell line (HepG2).

Publications

Fungal 7-epi-10-deacetyltaxol produced by an endophytic Pestalotiopsis microspora induces apoptosis in human hepatocellular carcinoma cell line (HepG2).

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