Ecdysteroids sensitize MDR and non-MDR cancer cell lines to doxorubicin, paclitaxel, and vincristine but tend to protect them from cisplatin
Open accessAbstract
Ecdysteroids, analogs of the insect molting hormone, are known for their various mild, nonhormonal bioactivities in mammals. Previously, we reported that less-polar ecdysteroids can modulate the doxorubicin resistance of a multidrug resistant (MDR) mouse lymphoma cell line expressing the human ABCB1 transporter. Here, we describe the ability of 20-hydroxyecdysone (1) and its mono- (2) and diacetonide (3) derivatives to sensitize various MDR and non-MDR cancer cell lines towards doxorubicin, paclitaxel, vincristine, or cisplatin. Drug IC50 values with or without ecdysteroid were determined by MTT assay. Compound 3 significantly sensitized all cell lines to each chemotherapeutic except for cisplatin, whose activity was decreased. In order to overcome solubility and stability issues for the future in vivo administration of compound 3, liposomal formulations were developed. By means of their combination index values obtained via checkerboard microplate method, a formulation showed superior activity to that of compound 3 alone. Because ecdysteroids act also on non-ABCB1 expressing (sensitive) cell lines, our results demonstrate that they do not or not exclusively exert their adjuvant anticancer activity as ABCB1 inhibitors, but other mechanisms must be involved, and they opened the way towards their in vivo bioactivity testing against various cancer xenografts.
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Several studies described ecdysterone-induced sensitization of cancer cells to genotoxic drugs and reduction of tumors in mice.
“It is interesting to note that despite the reported anabolic properties of ecdysterone regarding sport performance, several studies described ecdysterone-induced sensitization of cancer cells to genotoxic drugs and reduction of tumors in mice (Konovalova et al., 2002; Martins et al., 2015).”
From An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms (2020) · cites this paper as Martins et al., 2015
Ecdysterone made both drug-resistant and non-drug-resistant cancer cells more susceptible to doxorubicin treatment.
“Our results are in accordance with other studies (Konovalova et al., 2002; Martins et al., 2012; Martins et al., 2015) that have shown that ecdysterone made both drug-resistant and non-drug-resistant cancer cells more susceptible to doxorubicin treatment.”
From An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms (2020) · cites this paper as Martins et al., 2015
PEs exhibit toxicity against mouse T-cell lymphoma cells and their subcell line transfected with retrovirus overexpressing the ABCB1 efflux pump.
“PEs exhibit their toxicity against mouse T-cell lymphoma cells and their subcell line transfected with retrovirus overexpressing the ABCB1 efflux pump.”
From Phytoecdysteroids: Distribution, Structural Diversity, Biosynthesis, Activity, and Crosstalk with Phytohormones (2022) · cites this paper as [121]
PEs inhibit cell proliferation and rhodomine efflux associated with the ABCB1 transporter.
“PEs inhibit cell proliferation and rhodomine efflux associated with the ABCB1 transporter [121,160].”
From Phytoecdysteroids: Distribution, Structural Diversity, Biosynthesis, Activity, and Crosstalk with Phytohormones (2022) · cites this paper as [121]
20E may possess antineoplastic activity.
“Recent studies have shown that 20E may also possess antineoplastic activity.”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [14]
20E and its derivatives sensitize breast cancer cells to genotoxic stress, induce autophagy, and attenuate multiple drug resistance.
“We and others have shown that 20E and its derivates sensibilize breast cancer cells to genotoxic stress, induce autophagy, and attenuate multiple drug resistance [12,13,14,15,16,17,18,19].”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [14]
20E and its derivatives modulate the resistance of cancer cells to genotoxic drugs and mitigate multidrug resistance.
“Furthermore, it has been shown previously that 20E and its derivates modulate the resistance of cancer cells to genotoxic drugs and mitigate multidrug resistance [12,13,14,15,16,17,18,19].”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [14]
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“[63] Effect of 20HE and ecdysteroid fraction isolated from Serratula coronata L. on human blood cells and neutrophils.”
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Self-citation
- Authors
- Martins, A., Sipos, P., Dér, K., Csábi, J., Miklos, W., Berger, W., Zalatnai, A., Amaral, L., Molnár, J., Szabó-Révész, P., & Hunyadi, A.
- Affiliations
- University of Szeged (HU)
- Comprehensive Cancer Center Vienna (AT)
- University of Vienna (AT)
- Semmelweis University (HU)
- Universidade Nova de Lisboa (PT)
- Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, Szeged 6720, Hungary
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Eötvös Ucta 6, Szeged 6720, Hungary
- Corresponding author
- Hunyadi, Attila
- Venue
- BioMed Research International
- Publisher
- Wiley
- Published
- 2015
- Volume
- 2015
- Pages
- 1-8
- ISSN
- 1110-7243 (ISSN-L)
- 2314-6133
- 2314-6141
- PMC
- PMC4449901
- OpenAlex
- W1522518274
- Cited by
- 27
- References
- 18
- Citations by year
- 2026: 4 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 1
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- BioMed Research International (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Foundation for Cancer Research, Szeged (4.2.2.A-11/1/KONV-2012-0035)
- European Social Fund (4.2.2.A-11/1/KONV-2012-0035)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
- Keywords
- ecdysteroids, 20-hydroxyecdysone, multidrug resistance, P-glycoprotein, doxorubicin, paclitaxel, vincristine, cisplatin, chemosensitization, liposomal formulation, combination index, anticancer agents
- MeSH terms
- Animals, Cisplatin, Doxorubicin, Humans, Neoplasms, Paclitaxel, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Xenograft Model Antitumor Assays, Ecdysteroids, Mice, MCF-7 Cells
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