Cyclotides Chemosensitize Glioblastoma Cells to Temozolomide.

J Nat Prod

Institute for Ethnomedicine, Brain Chemistry Laboratories, Box 3464, Jackson, Wyoming 83001, United States.

Published: January 2022

Glioblastoma multiforme (GBM) is the most aggressive cancer originating in the brain, with a median survival of 12 months. Most patients do not respond to or develop resistance to the only effective chemotherapeutic drug, temozolomide (TMZ), used to treat gliomas. Novel treatment methods are critically needed. Cyclotides are plant peptides that may be promising adjuvants to TMZ chemotherapy. They exhibit antitumor activity and chemosensitize cells to doxorubicin in breast cancer studies. During this research, we optimized cyclotide isolation techniques, and several cyclotides (CyO2, CyO13, kalata B1, and varv peptide A) exhibited dose-dependent cytotoxicity in MTT assays with IC values of 2.15-7.92 μM against human brain astrocytoma cells (U-87 MG) and human bone marrow derived neuroblastoma cells (SH-SY5Y). CyO2 and varv peptide A increased TMZ-induced cell death in U-87 MG cultures alone and when coexposed with CyO2 or varv peptide A plus TMZ. Phase contrast microscopy of glioblastoma cells exposed to cyclotides alone and coexposed to TMZ indicated shrunken, granular cells with blebbing, and the most pronounced effects were observed with coexposure treatments of cyclotides and TMZ. Cumulative results provide the proof-of-concept that cyclotides may enhance TMZ chemotherapy, and pharmacokinetic investigations of cyclotides are warranted with respect to GBM.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.1c00595DOI Listing

Publication Analysis

Top Keywords

varv peptide
12
glioblastoma cells
8
tmz chemotherapy
8
cyo2 varv
8
cyclotides
7
cells
6
tmz
6
cyclotides chemosensitize
4
chemosensitize glioblastoma
4
cells temozolomide
4

Similar Publications

The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity.

Emerg Microbes Infect

December 2024

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.

The (OPXV) genus of the includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs.

View Article and Find Full Text PDF

High-throughput microfluidic chip with silica gel-C18 channels for cyclotide separation.

Anal Bioanal Chem

November 2023

Cellular Therapy and Stem Cell Production Application and Research Center (ESTEM), Eskişehir Osmangazi University, Eskişehir, Turkey.

Over the past two decades, microfluidic-based separations have been used for the purification, isolation, and separation of biomolecules to overcome difficulties encountered by conventional chromatography-based methods including high cost, long processing times, sample volumes, and low separation efficiency. Cyclotides, or cyclic peptides used by some plant families as defense agents, have attracted the interest of scientists because of their biological activities varying from antimicrobial to anticancer properties. The separation process has a critical impact in terms of obtaining pure cyclotides for drug development strategies.

View Article and Find Full Text PDF

Cyclotides Chemosensitize Glioblastoma Cells to Temozolomide.

J Nat Prod

January 2022

Institute for Ethnomedicine, Brain Chemistry Laboratories, Box 3464, Jackson, Wyoming 83001, United States.

Glioblastoma multiforme (GBM) is the most aggressive cancer originating in the brain, with a median survival of 12 months. Most patients do not respond to or develop resistance to the only effective chemotherapeutic drug, temozolomide (TMZ), used to treat gliomas. Novel treatment methods are critically needed.

View Article and Find Full Text PDF

Cyclotides are an extremely stable class of peptides, ubiquitously distributed in Violaceae. The aim of the present study was to investigate the presence of cyclotides in Sri Lankan Violaceae plants, using combined tools of transcriptomics and mass spectrometry. New cyclotides were discovered for the first time in the wild flora of Sri Lanka, within Viola betonicifolia, a plant used in traditional medicine as an antimicrobial.

View Article and Find Full Text PDF

The poxviruses are large, linear, double-stranded DNA viruses about 130 to 230 kbp, that have an animal origin and evolved to infect a wide host range. Variola virus (VARV), the causative agent of smallpox, is a poxvirus that infects only humans, but other poxviruses such as monkey poxvirus and cowpox virus (CPXV) have crossed over from animals to infect humans. Therefore understanding the biology of poxviruses can devise antiviral strategies to prevent these human infections.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!