Development of novel radiochemotherapy approaches targeting prostate tumor progenitor cells using nanohybrids

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Many tumors including prostate cancer are maintained by cancer stem cells (CSCs), which might cause tumor relapse if not eradicated during the course of treatment. Specific targeting or radiosensitization of CSCs bear promise to improve tumor curability by synergistic effects in combination with radiotherapy. Carbon nanotubes (CNTs) can be used as promising drug delivery systems for anticancer drugs such as the flavonoid catechin. Catechin is an extensively studied active ingredient of the different plants, including green tea, and it is widely recognized as co-adjuvant in cancer therapy. Here we describe the synthesis of biocompatible, catechin-loaded and gelatin-conjugated CNTs (Gel_CT_CNTs) with anticancer properties and demonstrate their potential for the eradication of prostate CSCs in combination with X-ray irradiation. Gel_CT_CNTs showed a significant enhancement of in vitro anticancer activity as compared to catechin alone. Moreover, treatment of prostate cancer cells with Gel_CT_CNT nanohybrids inhibited the tumorigenic cell population defined by a high aldehyde dehydrogenase (ALDH) activity. A combination of X-ray irradiation and treatment with Gel_CT_CNTs caused a decrease in the protein level of stem cell-related transcription factors and regulators including Nanog, Oct4 and β-catenin and led to an increase of cancer cell radiosensitivity as demonstrated by clonogenic and spherogenic cell survival assays. Taken together, our results suggest that a combination of irradiation and Gel_CT_CNTs can be potentially used for the radiosensitization and eradication of prostate CSC populations.

Details

Original languageEnglish
Pages (from-to)2492-2503
Number of pages12
JournalInternational Journal of Cancer
Volume137
Issue number10
Publication statusPublished - 15 Nov 2015
Peer-reviewedYes

External IDs

Scopus 84941944139
researchoutputwizard legacy.publication#67794
PubMed 26059723
researchoutputwizard legacy.publication#68000
ORCID /0000-0003-3717-3637/work/141545156
ORCID /0000-0002-5247-908X/work/142241921

Keywords

Sustainable Development Goals

Keywords

  • Aldehyde Dehydrogenase/metabolism, Animals, Antineoplastic Agents/administration & dosage, Catechin/chemistry, Cell Line, Tumor, Cell Proliferation, Chemoradiotherapy/methods, Drug Compounding, Gelatin/chemistry, Gene Expression Regulation, Neoplastic/drug effects, Humans, Male, Mice, Nanotubes, Carbon/chemistry, Neoplasm Transplantation, Neoplastic Stem Cells/drug effects, Prostatic Neoplasms/pathology, Radiation-Sensitizing Agents/administration & dosage