Proapoptotic and proautophagic activity of 20-hydroxyecdysone in breast cancer cells in vitro
Abstract
The present study was designed to identify the biological activity of three ecdysones, i.e., 20-hydroxyecdysone (20-HE), ajugasterone C, and polypodine B isolated from Serratula coronata. The main objective was to investigate the molecular mechanism of the biological activity of those compounds and to assess their impact on breast cancer cell survival and cell cycle. Cell lines were selected according to their hormone receptor status since this factor is perceived as a crucial one in the cancer prognosis as well as cancer cell response to therapy. Consequently, MCF7 (ER/PR+, HER2-), T-47D (ER/PR+, HER2-/+), and MDA-MB-231 (ER/PR-, HER2-) were enrolled in the study. Additionally, a non-tumorigenic, MCF10A cells were selected to verify any potential specificity to cancer cells. Interestingly, none of the studied compounds affected the viability of MCF10A cells while cancer cells were altered, albeit in different ways. Polypodine B did not affect the viability or cell cycle distribution of studied breast cancer cells. By contrast, 20-HE and ajugasterone C significantly inhibited the viability of triple-negative cell line, MDA-MB-231. Interestingly, 20-HE revealed proapoptotic activity in MDA-MB-231 and T-47D cells that was manifested by alterations in PARP, Bax, and Bcl-2 levels as well as caspase-3 activation. Moreover, 20-HE induced autophagy that was mediated by modification of autophagy-associated proteins, i.e., LC3, p62, and mTOR, but only in MDA-MB-231 cells. This study is the first to report diverse biological activity of phytoecdysones in different breast cancer cells, that suggests association with molecular characteristics including receptor status but also other biological properties and genetic markers.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The selective effect of 20E on triple receptor-negative breast cancer cells was manifested by pro-apoptotic activity altering PARP, Bax, Bcl-2, and caspase 3 activity and induction of autophagy-associated proteins.
“This effect was manifested by pro-apoptotic activity altering PARP, Bax, Bcl-2, and caspase 3 activity and induction of autophagy-associated proteins.”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [64]
20E selectively decreased viability in a triple receptor-negative breast cancer cell line in contrast to other breast cancer cells and non-cancerous controls.
“20E selectively decreased viability in a triple receptor-negative breast cancer cell line in contrast to other breast cancer cells and non-cancerous controls [64].”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [64]
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 [16]
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 [16]
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 [16]
Cites
1 retracted
RETRACTED: Regulation of cell proliferation and migration by p62 through stabilization of Twist1
Qiang, L., Zhao, B., Ming, M., Wang, N., He, T., Hwang, S., Thorburn, A. M., & He, Y. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322913111 · Cited by 215 · see citing works
RetractedApoptosis: A Target for Anticancer Therapy
Pfeffer, C. M., & Singh, A. T. K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020448 · Cited by 1,558 · see citing works
The Role of Autophagy in Cancer: Therapeutic Implications
Yang, Z. J., Chee, C. E., Huang, S., & Sinicrope, F. A. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0047 · Cited by 1,217 · see citing works
The Roles of Autophagy in Cancer
Yun, C. W., & Lee, S. H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113466 · Cited by 965 · see citing works
The pros and cons of phytoestrogens
Patisaul, H. B., & Jefferson, W. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.03.003 · Cited by 746 · see citing works
Autophagy and multidrug resistance in cancer
Li, Y., Lei, Y., Yao, N., Wang, C., Hu, N., Ye, W., Zhang, D., & Chen, Z. (2017) · 癌症：英文版 · doi:10.1186/s40880-017-0219-2 · Cited by 667 · see citing works
The Signaling Adaptor p62 Is an Important NF-κB Mediator in Tumorigenesis
Duran, A., Linares, J. F., Galvez, A. S., Wikenheiser, K., Flores, J. M., Diaz-Meco, M. T., & Moscat, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.02.001 · Cited by 541 · see citing works
p62 Is a Key Regulator of Nutrient Sensing in the mTORC1 Pathway
Durán, Á., Amanchy, R., Linares, J. F., Joshi, J. P., Abu‐Baker, S., Porollo, A., Hansen, M., Moscat, J., & Díaz-Meco, M. T. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.038 · Cited by 502 · see citing works
Phytoecdysteroids: Biological aspects
Dinan, L. (2001) · Phytochemistry · doi:10.1016/s0031-9422(01)00078-4 · Cited by 392 · see citing works
Autophagic Regulation of p62 is Critical for Cancer Therapy
Islam, M. A., Sooro, M. A., & Zhang, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051405 · Cited by 234 · see citing works
Phytoecdysteroids and Anabolic Androgenic Steroids--Structure and Effects on Humans
Bathori, M., Toth, N., Hunyadi, A., Marki, A., & Zador, E. (2008) · Current Medicinal Chemistry · doi:10.2174/092986708783330674 · Cited by 201 · see citing works
Practical uses for ecdysteroids in mammals including humans: and update
Lafont, R., & Dinan, L. (2003) · Journal of Insect Science · doi:10.1093/jis/3.1.7 · Cited by 196 · see citing works
Practical uses for ecdysteroids in mammals including humans: And update
Lafont, R., & Dinan, L. (2003) · Journal of Insect Science · doi:10.1673/031.003.0701 · Cited by 196 · see citing works
Estrogenic activity of phenol red
Welshons, W. V., Wolf, M. F., Murphy, C. S., & Jordan, V. C. (1988) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(88)90072-x · Cited by 176 · see citing works
Phytoecdysteroids increase protein synthesis in skeletal muscle cells.
Gorelick-Feldman, J., MacLean, D., Ilic, N., Poulev, A., Lila, M. A., Cheng, D., & Raskin, I. (2008) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf073059z · Cited by 166 · see citing works
Cancer Chemopreventive Agents (Antitumor-promoters) from <i>Ajuga </i><i>d</i><i>ecumbens</i>
Takasaki, M., Tokuda, H., Nishino, H., & Konoshima, T. (1999) · Journal of Natural Products · doi:10.1021/np990033w · Cited by 83 · see citing works
Removal of serum factors by charcoal treatment promotes adipogenesis via a MAPK-dependent pathway
Dang, Z., & Löwik, C. W. G. M. (2005) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-005-3857-7 · Cited by 60 · see citing works
Hunyadi, A., Herke, I., Lengyel, K., Báthori, M., Kele, Z., Simon, A., Tóth, G., & Szendrei, K. (2016) · Scientific Reports · doi:10.1038/srep37322 · Cited by 59 · see citing works
Jiang, Q., Zheng, S., & Wang, G. (2013) · Future Medicinal Chemistry · doi:10.4155/fmc.13.63 · Cited by 48 · see citing works
Lisiak, N., Paszel-Jaworska, A., Bednarczyk–Cwynar, B., Zaprutko, L., Kaczmarek, M., & Rybczyńska, M. (2013) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2013.11.009 · Cited by 44 · see citing works
Self-citationAka, J. A., & Lin, S. (2012) · PLoS ONE · doi:10.1371/annotation/18f08a33-35e1-4bf9-8d21-476757dccbef · Cited by 42 · see citing works
Ecdysteroids: one potential new anabolic family in breeding animals
Le Bizec, B., Antignac, J.-P., Monteau, F., & Andre, F. (2002) · Analytica Chimica Acta · doi:10.1016/s0003-2670(02)00874-7 · Cited by 41 · see citing works
Mostrom, M. S., & Evans, T. J. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-382032-7.10052-9 · Cited by 37 · see citing works
Cytostatic and Cytotoxic Natural Products against Cancer Cell Models
Ling, T., Lang, W. H., Maier, J., Centurion, M. Q., & Rivas, F. (2019) · Molecules · doi:10.3390/molecules24102012 · Cited by 36 · see citing works
Hunyadi, A., Csábi, J., Martins, A., Molnár, J., Balázs, A., & Tóth, G. (2017) · Molecules · doi:10.3390/molecules22020199 · Cited by 31 · see citing works
Martins, A., Csábi, J., Balázs, A., Kitka, D., Amaral, L., Molnár, J., Simon, A., Tóth, G., & Hunyadi, A. (2013) · Molecules · doi:10.3390/molecules181215255 · Cited by 30 · see citing works
Shuvalov, O., Fedorova, O., Tananykina, E., Gnennaya, Y., Daks, A., Petukhov, A., & Barlev, N. A. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.561537 · Cited by 30 · see citing works
Badowska-Kozakiewicz, A. M., Patera, J., Sobol, M., & Przybylski, J. (2015) · Współczesna Onkologia · doi:10.5114/wo.2015.51826 · Cited by 28 · see citing works
Phytoecdysteroids of Silene guntensis and their in vitro cytotoxic and antioxidant activity
Mamadalieva, N. Z., El-Readi, M. Z., Janibekov, A. A., Tahrani, A., & Wink, M. (2011) · Zeitschrift für Naturforschung C · doi:10.1515/znc-2011-5-604 · Cited by 24 · see citing works
Martucciello, S., Paolella, G., Музашвили, Т. С., Схиртладзе, А. В., Pìzza, C., Caputo, I., & Piacente, S. (2017) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2017.11.002 · Cited by 24 · see citing works
Ecdysteroid derivatives that reverse P-glycoprotein-mediated drug resistance
Bortolozzi, R., Luraghi, A., Mattiuzzo, E., Sacchetti, A., Silvani, A., & Viola, G. (2020) · Journal of Natural Products · doi:10.1021/acs.jnatprod.0c00334 · Cited by 21 · see citing works
Konovalova (2002) · Biology Bulletin · doi:10.1023/a:1021755622981 · Cited by 20 · see citing works
Ju, Y., Liang, H., Du, K., Guo, Z., & Meng, D. (2020) · Natural Product Research · doi:10.1080/14786419.2020.1805603 · Cited by 20 · see citing works
Dinan, L. N., Savchenko, T., & Whiting, P. (2002) · Biochemical Systematics and Ecology · doi:10.1016/s0305-1978(01)00068-0 · Cited by 17 · see citing works
Pavela, R., Harmatha, J., Bárnet, M., & Vokáč, K. (2005) · European Journal of Entomology · doi:10.14411/eje.2005.091 · Cited by 17 · see citing works
Chemical constituents of <i>Silene montbretiana</i>
Kılınç, H., Masullo, M., Bottone, A., Karayıldırım, T., Alankuş, Ö., & Piacente, S. (2019) · Natural Product Research · doi:10.1080/14786419.2018.1451998 · Cited by 14 · see citing works
Stereochemistry of Hydride Reduction of 20-Hydroxyecdysone Derivatives
Одиноков, В. Н., Савченко, Р. Г., Shafikov, R. V., Афонькина, С. Р., Khalilov, L. M., Качала, В. В., & Shashkov, A. S. (2005) · Russian Journal of Organic Chemistry · doi:10.1007/s11178-005-0338-0 · Cited by 13 · see citing works
Lisiak, N., Totoń, E., Rubiś, B., Majer, B., & Rybczyńska, M. (2016) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520616666160223114104 · Cited by 11 · see citing works
Self-citationAnti-estrogen-resistant breast cancer cells are sensitive to cisplatin plus TRAIL treatment
Yin, S., Rishi, A. K., & Reddy, K. B. (2015) · Oncology Reports · doi:10.3892/or.2015.3721 · Cited by 9 · see citing works
Urbańska, M. (2014) · Journal of Plant Sciences · doi:10.11648/j.jps.20140205.16 · Cited by 6 · see citing works
Autophagy, new perspectives in anticancer therapy
Lisiak, N., Totoń, E., & Rybczyńska, M. (2014) · Postępy Higieny i Medycyny Doświadczalnej · doi:10.5604/17322693.1111361 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Todorova, V., Ivanov, K., & Ivanova, S. (2021) · Plants · doi:10.3390/plants11010064 · Cited by 56 · see citing works
Ecdysteroids: Isolation, Chemical Transformations, and Biological Activity
Savchenko, R. G., Veskina, N. A., Odinokov, V. N., Benkovskaya, G. V., & Parfenova, L. V. (2022) · Phytochemistry Reviews · doi:10.1007/s11101-021-09792-y · Cited by 39 · see citing works
Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition
Todorova, V., Ivanova, S., Chakarov, D., Kraev, K., & Ivanov, K. (2024) · Nutrients · doi:10.3390/nu16091382 · Cited by 31 · see citing works
“[66] Interaction between the ecdysterone isolated from Sesuvium portulacastrum and nitric oxide synthase.”
BackgroundShuvalov, O., Kirdeeva, Y., Fefilova, E., Netsvetay, S., Zorin, M., Vlasova, Y., Fedorova, O., Daks, A., Parfenyev, S., & Barlev, N. (2023) · Metabolites · doi:10.3390/metabo13050656 · Cited by 21 · see citing works
Baev, A. Y., Charishnikova, O. S., Khasanov, F. A., Nebesnaya, K. S., Makhmudov, A. R., Rakhmedova, M. T., Khushbaktova, Z. A., Syrov, V. N., & Levitskaya, Y. V. (2022) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2022.106066 · Cited by 16 · see citing works
Park, M. N., Choi, J., Fahim, M. M. H., Asevedo, E. A., Nurkolis, F., Ribeiro, R. I. M. D. A., Kang, H. N., Kang, S., Syahputra, R. A., & Kim, B. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1504618 · Cited by 14 · see citing works
Anti-Adipogenic Activity of Rhaponticum carthamoides and Its Secondary Metabolites
Todorova, V., Savova, M. S., Ivanova, S., Ivanov, K., & Georgiev, M. I. (2023) · Nutrients · doi:10.3390/nu15133061 · Cited by 12 · see citing works
Zhang, K., Zhou, Z., Wang, C., Yu, M., Zhang, Y., Shi, Y., Wang, X., Liu, Y., Xu, L., Shi, W., et al. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/2624434 · Cited by 12 · see citing works
Zádor, E. (2025) · Cells · doi:10.3390/cells14060431 · Cited by 9 · see citing works
“Curiously enough, 20E selectively decreased viability in a triple receptor-negative breast cancer cell line in contrast to other breast cancer cells and non-cancerous controls [64].”
Gu, H., Zou, H., Cheng, J., Liu, X., Jiang, Z., Peng, P., Li, F., & Li, B. (2024) · Insect Molecular Biology · doi:10.1111/imb.12911 · Cited by 12 · see citing works
Wang, Z., Wu, F., Ju, Y., Liang, L., Chang, F.-J., Dong, M., Diao, J., & Wu, H.-Y. (2025) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.70446 · Cited by 9 · see citing works
Kumar, P., Singh, K., Lone, J. F., Bhushan, A., Gupta, P., & Gairola, S. (2023) · Pharmacognosy Magazine · doi:10.1177/09731296221145070 · Cited by 9 · see citing works
Mamadalieva, N. Z., Koval, A., Dusmuratov, M. M., Hussain, H., & Katanaev, V. L. (2024) · Biomolecules · doi:10.3390/biom14101285 · Cited by 8 · see citing works
Todorova, V., Ivanova, S., Yotov, V., Zaytseva, E., Ardasheva, R., Turiyski, V., Prissadova, N., & Ivanov, K. (2024) · Molecules · doi:10.3390/molecules29215145 · Cited by 7 · see citing works
Sripinyowanich, S., Petchsri, S., Tongyoo, P., Lee, T., Lee, S., & Cho, W. K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032397 · Cited by 7 · see citing works
Hu, J., Feng, Y., Li, B., Wang, F., Qian, Q., Tian, W., Niu, L., & Wang, X. (2023) · PeerJ · doi:10.7717/peerj.15948 · Cited by 6 · see citing works
Ma, Q., Wu, F., Liu, X., Zhao, C., Sun, Y., Li, Y., Zhang, W., Ju, H., & Wang, Y. (2024) · Translational Oncology · doi:10.1016/j.tranon.2024.101958 · Cited by 5 · see citing works
Li, X., Qin, L., Sun, Y., Zou, K., Zhao, C., Xiao, M., Yan, S., Zhang, X., Shen, Y., Tian, L., et al. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.120842 · Cited by 5 · see citing works
Neuroprotective Effect of Mas Activation by BIO101 in Vincristine‐Induced Small Fiber Neuropathy
Frachet, S., Danigo, A., Latil, M., Dilda, P. J., Bessaguet, F., Richard, L., Sturtz, F. G., Magy, L., & Demiot, C. (2025) · Journal of the Peripheral Nervous System · doi:10.1111/jns.70055 · Cited by 2 · see citing works
Isolation of Phytoecdysteroids: Ajugasterone C and 20-Hydroxyecdysone, from Sida alba Linn.
Ezennaka, C. N., Srivedavyasasri, R., Izunobi, J. U., Mallen, J. J., Sofidiya, M. O., Asekun, O. T., Igbokwe, N. H., Nkwocha, S. T., & Ross, S. A. (2026) · ACS Omega · doi:10.1021/acsomega.5c11934 · Cited by 1 · see citing works
The Effect of 20-Hydroxyecdysone on the Functioning of Isolated Mouse Skeletal Muscle Mitochondria
Semenova, A. A., Igoshkina, A. D., Mikina, N. V., Савченко, Р. Г., Parfenova, L. V., & Dubinin, M. V. (2024) · Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology · doi:10.1134/s1990747824700144 · Cited by 1 · see citing works
The Effect of 20-Hydroxyecdysone on the Functioning of isolated Mouse Skeletal Muscle Mitochondria
Semenova, A. A., Igoshkina, A. D., Mikina, N. V., Савченко, Р. Г., Parfenova, L. V., & Dubinin, M. V. (2024) · Биологические мембраны Журнал мембранной и клеточной биологии · doi:10.31857/s0233475524030067
Kirdeeva, Y. N., Fefilova, E. A., Daks, A. A., Parfenyev, S. E., Fedorova, O., Барлев, Н. А., & Shuvalov, O. Y. (2024) · Cell and Tissue Biology · doi:10.1134/s1990519x24700561
Kılıçcıoğlu, İ., Dülger, G., & Dülger, B. (2025) · Online Türk Sağlık Bilimleri Dergisi · doi:10.26453/otjhs.1685503
Pharmacokinetic and Safety Profiles of Phytoecdysteroids in Mammals
Dinan, L. N., & Lafont, R. (2026) · Springer eBooks · doi:10.1007/978-981-95-8423-9_7
Metabolic and Hormonal Modulation by Phytoecdysteroids in Mammals
Lafont, R. (2026) · Springer eBooks · doi:10.1007/978-981-95-8423-9_3
Zhang, J., Wei, C., Wang, D., He, R., Xiao, X., Xu, J., & Lu, J. (2026) · Frontiers in Bioscience-Landmark · doi:10.31083/fbl52978
- Authors
- Romaniuk-Drapała, A., Lisiak, N., Totoń, E., Matysiak, A., Nawrot, J., Nowak, G., Kaczmarek, M., Rybczyńska, M., & Rubiś, B.
- Affiliations
- Poznan University of Medical Sciences (PL)
- Corresponding author
- Lisiak, Natalia
- ORCID
- Venue
- Chemico-Biological Interactions
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 342
- Pages
- 109479
- ISSN
- 0009-2797 (ISSN-L)
- OpenAlex
- W3156731951
- Cited by
- 27
- References
- 41
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 5 · 2022: 3 · 2021: 1
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Chemico-Biological Interactions (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu (502\u201301\u201303318432\u201302496, 03318432, 02496)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical Studies and Bioactivities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Sesquiterpenes and Asteraceae Studies
- Keywords
- 20-hydroxyecdysone, polypodine B, Serratula coronata, phytoecdysone, breast cancer, apoptosis, autophagy, triple-negative breast cancer, MDA-MB-231 cells, T-47D, MCF-7 cells, cell cycle, hormone receptor status, caspase-3, Bax, Bcl-2, LC3, p62, mTOR
- MeSH terms
- Antineoplastic Agents, Autophagy, Breast Neoplasms, Drug Screening Assays, Antitumor, Ecdysterone, Humans, Apoptosis, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
