STEROIDAL ALKALOIDS FROM SOLANACEAE SPECIES IN HEMATOLOGICAL MALIGNANCIES: MECHANISMS AND THERAPEUTIC POTENTIAL

Authors

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5084

Keywords:

Glycoalkaloids (GAS), Steroidal Alkaloids, Solanine, Leukemia, Hematological Oncology, Multidrug Resistance (MDR)

Abstract

Background: Hematological malignancies remain a substantial contributor to global cancer morbidity and mortality, and as such – a major public health issue. Recent evidence has revealed that Solanaceae alkaloids (SAs) could contribute to developing new treatment strategies in hematological oncology.

Objective: To critically evaluate contemporary evidence on the anti-cancer effects of SAs, including alpha-solanine, solanidine, solasodine, solamargine, tomatine and tomatidine as well as their potential applicability as bioactive compounds in hematology-related research and therapy.

Methods: This narrative review was informed by studies retrieved from widely recognized search engines and databases, including PubMed/MedLine, Google Scholar, ScienceDirect, Wiley, Scopus and Springer Link. The search was conducted using the following MeSH terms: “Solanaceae Alkaloids”, “Solanine”, “Solanidine”, “Solasodine”, “Solamargine”, “Tomatine”, “Tomatidine”, “Leukemia”, “Lymphoma”, “Hematology” and "Blood cancer". Original English-language studies published between 2005 and 2025 were included. Case reports and non-primary data sources were excluded. No meta-analysis was performed.

Results: Steroidal alkaloids from Solanaceae species demonstrate significant cytotoxic and anti-proliferative effects against various leukemia and lymphoma cell lines. These compounds have the capacity to inhibit tumor growth and survival through multiple mechanisms, including the induction of apoptosis, oncosis, and cell cycle arrest.

Conclusions: Solanaceae-derived steroidal alkaloids exhibit promising antitumor activity in hematological malignancies by modulating apoptosis, survival signaling pathways, and mechanisms of drug resistance. Their ability to enhance chemosensitivity supports further investigation as potential therapeutic or adjuvant agents, pending validation in in vivo and clinical studies.

References

Asgaritarghi, G., Farsani, S. S. M., Sadeghizadeh, D., Najafi, F., & Sadeghizadeh, M. (2023). Anti-cancer role of dendrosomal nano solanine in chronic myelogenous leukemia cell line through attenuation of PI3K/AKT/mTOR signaling pathway and inhibition of hTERT expression. Current Molecular Pharmacology, 16(5), 592–608. https://doi.org/10.2174/1874467215666220516143155

Ayvaz, H. B., Yenigül, M., & Gencer Akçok, E. B. (2024). Tomatidine, a steroidal alkaloid, synergizes with cisplatin to inhibit cell viability and induce cell death selectively on FLT3-ITD+ acute myeloid leukemia cells. Cell Biochemistry and Biophysics, 82(3), 2889–2900. https://doi.org/10.1007/s12013-024-01406-6

Braga, T. V., Evangelista, F. C. G., Gomes, L. C., Araújo, S. S. D. S., Carvalho, M. D. G., & Sabino, A. P. (2017). Evaluation of MiR-15a and MiR-16-1 as prognostic biomarkers in chronic lymphocytic leukemia. Biomedicine & Pharmacotherapy, 92, 864–869. https://doi.org/10.1016/j.biopha.2017.05.144

Chao, M. W., Chen, C. H., Chang, Y. L., Teng, C. M., & Pan, S. L. (2012). α-Tomatine-mediated anti-cancer activity in vitro and in vivo through cell cycle- and caspase-independent pathways. PLOS ONE, 7(9), e44093. https://doi.org/10.1371/journal.pone.0044093

Chen, Y., Li, S., Sun, F., Han, H., Zhang, X., Fan, Y., & Zhou, Y. (2010). In vivo antimalarial activities of glycoalkaloids isolated from Solanaceae plants. Pharmaceutical Biology, 48(9), 1018–1024. https://doi.org/10.3109/13880200903440211

Cheng, X., Narisawa, M., Jin, E., & Li, X. (2017). α-Solanine as potential therapeutic target in pulmonary artery hypertension. Journal of Hypertension, 35(12), 2377–2379. https://doi.org/10.1097/HJH.0000000000001483

Chiacchiera, F., & Simone, C. (2010). The AMPK-FoxO3A axis as a target for cancer treatment. Cell Cycle, 9(6), 1091–1096. https://doi.org/10.4161/cc.9.6.11035

Darici, S., Alkhaldi, H., Horne, G., Jørgensen, H. G., Marmiroli, S., & Huang, X. (2020). Targeting PI3K/Akt/mTOR in AML: Rationale and clinical evidence. Journal of Clinical Medicine, 9(9), 2934. https://doi.org/10.3390/jcm9092934

El-Daly, S. M., Gouhar, S. A., Gamal-Eldeen, A. M., Abdel Hamid, F. F., Ashour, M. N., & Hassan, N. S. (2019). Synergistic effect of α-solanine and cisplatin induces apoptosis and enhances cell cycle arrest in human hepatocellular carcinoma cells. Anti-Cancer Agents in Medicinal Chemistry, 19(18), 2197–2210. https://doi.org/10.2174/1871520619666190930123520

Friedman, M. (2006). Potato glycoalkaloids and metabolites: Roles in the plant and in the diet. Journal of Agricultural and Food Chemistry, 54(23), 8655–8681. https://doi.org/10.1021/jf061471t

Friedman, M., Roitman, J. N., & Kozukue, N. (2003). Glycoalkaloid and calystegine contents of eight potato cultivars. Journal of Agricultural and Food Chemistry, 51(10), 2964–2973. https://doi.org/10.1021/jf021146f

Hanada, M., Delia, D., Aiello, A., Stadtmauer, E., & Reed, J. C. (1993). bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood, 82(6), 1820–1828.

Heftmann, E., Lieber, E. R., & Bennet, R. D. (1967). Phytochemistry, 6, 225.

Hlywka, J. J., Stephenson, G. R., Sears, M. K., & Yada, R. Y. (1994). Effects of insect damage on glycoalkaloid content in potatoes. Journal of Agricultural and Food Chemistry, 42, 2545–2550. https://doi.org/10.1021/jf00047a032

Huang, H., Chen, S., Van Doren, J., Li, D., Farichon, C., He, Y., Zhang, Q., Zhang, K., Conney, A. H., Goodin, S., Du, Z., & Zheng, X. (2015). α-Tomatine inhibits growth and induces apoptosis in HL-60 human myeloid leukemia cells. Molecular Medicine Reports, 11(6), 4573–4578. https://doi.org/10.3892/mmr.2015.3238

Huang, J., Wang, X., Pan, L., et al. (2023). ɑ-Solanine affects the apoptosis and angiogenesis of M2-like TAMs cells by regulating the PI3K/AKT/mTOR signaling pathway under hypoxia. Natural Product Communications, 18(7). https://doi.org/10.1177/1934578X231186273

Hus, I., Puła, B., & Robak, T. (2022). PI3K inhibitors for the treatment of chronic lymphocytic leukemia: Current status and future perspectives. Cancers, 14(6), 1571. https://doi.org/10.3390/cancers14061571

Isa, R., Horinaka, M., Tsukamoto, T., Mizuhara, K., Fujibayashi, Y., Taminishi-Katsuragawa, Y., Okamoto, H., Yasuda, S., Kawaji-Kanayama, Y., Matsumura-Kimoto, Y., Mizutani, S., Shimura, Y., Taniwaki, M., Sakai, T., & Kuroda, J. (2022). The rationale for the dual-targeting therapy for RSK2 and AKT in multiple myeloma. International Journal of Molecular Sciences, 23(6), 2919. https://doi.org/10.3390/ijms23062919

Kasnak, C., & Artik, N. (2018). Change in some glycoalkaloids of potato under different storage regimes. Potato Research, 61, 183–193. https://doi.org/10.1007/s11540-018-9367-2

Kunadt, D., Dransfeld, C., Dill, C., Schmiedgen, M., Kramer, M., Altmann, H., Röllig, C., Bornhäuser, M., Mahlknecht, U., Schaich, M., & Stölzel, F. (2020). Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia. Annals of Hematology, 99(9), 2173–2180. https://doi.org/10.1007/s00277-020-04163-7

Lafta, A. M., & Lorenzen, J. H. (2000). Influence of high temperature and reduced irradiance on glycoalkaloid levels in potato leaves. Journal of the American Society for Horticultural Science, 125, 563–566. https://doi.org/10.21273/JASHS.125.5.563

Li, Q. W., Zhang, G. L., Hao, C. X., Ma, Y. F., Sun, X., Zhang, Y., Cao, K. X., Li, B. X., Yang, G. W., & Wang, X. M. (2021). SANT, a novel Chinese herbal monomer combination, decreasing tumor growth and angiogenesis via modulating autophagy in heparanase overexpressed triple-negative breast cancer. Journal of Ethnopharmacology, 266, 113430. https://doi.org/10.1016/j.jep.2020.113430

Li, W., Liu, Y., Wei, M., Yang, Z., Tang, H., & Huang, W. (2025). Chondrocyte-targeted α-solanine through HIF-1α regulating glycolysis to reduce the ferroptosis of chondrocyte in osteoarthritis. International Immunopharmacology, 159, 114841. https://doi.org/10.1016/j.intimp.2025.114841

Ma, X., Li, Y., Liang, D., Jiang, F., Zhang, L., Song, W., Wan, B., Xia, C., & Lu, Q. (2024). Solanine induces ferroptosis in colorectal cancer cells through ALOX12B/ADCY4 molecular axis. Journal of Pharmacy and Pharmacology, 76(3), 224–235. https://doi.org/10.1093/jpp/rgad122

Meng, X. Q., Zhang, W., Zhang, F., Yin, S. Y., Xie, H. Y., Zhou, L., & Zheng, S. S. (2016). Solanine-induced reactive oxygen species inhibit the growth of human hepatocellular carcinoma HepG2 cells. Oncology Letters, 11(3), 2145–2151. https://doi.org/10.3892/ol.2016.4167

Mensinga, T. T., Sips, A. J., Rompelberg, C. J., van Twillert, K., Meulenbelt, J., van den Top, H. J., & van Egmond, H. P. (2005). Potato glycoalkaloids and adverse effects in humans: An ascending dose study. Regulatory Toxicology and Pharmacology, 41(1), 66–72. https://doi.org/10.1016/j.yrtph.2004.09.004

Milner, S. E., Brunton, N. P., Jones, P. W., O’Brien, N. M., Collins, S. G., & Maguire, A. R. (2011). Bioactivities of glycoalkaloids and their aglycones from Solanum species. Journal of Agricultural and Food Chemistry, 59, 3454–3484. https://doi.org/10.1021/jf200439q

Minorics, R., Szekeres, T., Krupitza, G., Saiko, P., Giessrigl, B., Wölfling, J., Frank, E., & Zupkó, I. (2011). Antiproliferative effects of some novel synthetic solanidine analogs on HL-60 human leukemia cells in vitro. Steroids, 76(1–2), 156–162. https://doi.org/10.1016/j.steroids.2010.10.006

Mohsenikia, M., Farhangi, B., Alizadeh, A. M., Khodayari, H., Khodayari, S., Khori, V., Arjmand Abbassi, Y., Vesovic, M., Soleymani, A., & Najafi, F. (2016). Therapeutic effects of dendrosomal solanine on a metastatic breast tumor. Life Sciences, 148, 260–267. https://doi.org/10.1016/j.lfs.2016.02.008

Nie, X., Dai, Y., Tan, J., Chen, Y., Qin, G., Mao, W., Zou, J., Chang, Y., Wang, Q., & Chen, J. (2017). α-Solanine reverses pulmonary vascular remodeling and vascular angiogenesis in experimental pulmonary artery hypertension. Journal of Hypertension, 35(12), 2419–2435. https://doi.org/10.1097/HJH.0000000000001475

Nielsen, S. D., Schmidt, J. M., Kristiansen, G. H., Dalsgaard, T. K., & Larsen, L. B. (2020). Liquid chromatography mass spectrometry quantification of α-solanine, α-chaconine, and solanidine in potato protein isolates. Foods, 9(4), 416. https://doi.org/10.3390/foods9040416

Osman, S. F. (1983). Glycoalkaloids in potatoes. Food Chemistry, 11(4), 235–247. https://doi.org/10.1016/0308-8146(83)90073-0

Pan, B., Zhong, W., Deng, Z., Lai, C., Chu, J., Jiao, G., Liu, J., & Zhou, Q. (2016). Inhibition of prostate cancer growth by solanine requires the suppression of cell cycle proteins and the activation of ROS/P38 signaling pathway. Cancer Medicine, 5(11), 3214–3222. https://doi.org/10.1002/cam4.916

Pan, T., Zhang, J., Wang, X., et al. (2021). Global burden and trends of hematologic malignancies based on Global Cancer Observatory 2022 and Global Burden of Disease. Experimental Hematology & Oncology, 14, 98. https://doi.org/10.1186/s40164-025-00684-x

Pekarsky, Y., Balatti, V., & Croce, C. M. (2018). BCL2 and miR-15/16: From gene discovery to treatment. Cell Death & Differentiation, 25(1), 21–26. https://doi.org/10.1038/cdd.2017.159

Percival, G., Dixon, G., & Sword, A. (1994). Glycoalkaloid concentration of potato tubers following continuous illumination. Journal of the Science of Food and Agriculture, 66, 139–144. https://doi.org/10.1002/jsfa.2740660206

Sandhöfer, N., Metzeler, K. H., Rothenberg, M., Herold, T., Tiedt, S., Groiß, V., Carlet, M., Walter, G., Hinrichsen, T., Wachter, O., Grunert, M., Schneider, S., Subklewe, M., Dufour, A., Fröhling, S., Klein, H. G., Hiddemann, W., Jeremias, I., & Spiekermann, K. (2015). Dual PI3K/mTOR inhibition shows antileukemic activity in MLL-rearranged acute myeloid leukemia. Leukemia, 29(4), 828–838. https://doi.org/10.1038/leu.2014.305

Shiyong, G., Yubin, J., Xiang, Z., & Chenfeng, J. (2007). Effects of solanine on the contents of Caspase-3 and Bcl-2 protein in HepG2 cells. In IEEE/ICME International Conference on Complex Medical Engineering (pp. 1689–1693). IEEE. https://doi.org/10.1109/ICCME.2007.4382035

Singh, B. (2016). Glycoalkaloids in peels of Indian potatoes. Potato Journal, 43(1). https://epubs.icar.org.in/index.php/PotatoJ/article/view/48534

Sun, L., Zhao, Y., Li, X., Yuan, H., Cheng, A., & Lou, H. (2010). A lysosomal-mitochondrial death pathway is induced by solamargine in human K562 leukemia cells. Toxicology in Vitro, 24(6), 1504–1511. https://doi.org/10.1016/j.tiv.2010.07.013

Sun, L., Zhao, Y., Yuan, H., Li, X., Cheng, A., & Lou, H. (2011). Solamargine, a steroidal alkaloid glycoside, induces oncosis in human K562 leukemia and squamous cell carcinoma KB cells. Cancer Chemotherapy and Pharmacology, 67(4), 813–821. https://doi.org/10.1007/s00280-010-1387-9

Tang, X., Guo, Y., Zhang, S., Wang, X., Teng, Y., Jin, Q., Jin, Q., Shen, W., & Wang, R. (2023). Solanine represses gastric cancer growth by mediating autophagy through AAMDC/MYC/ATF4/Sesn2 signaling pathway. Drug Design, Development and Therapy, 17, 389–402. https://doi.org/10.2147/DDDT.S389764

Teli, D. M., Shah, M. B., & Chhabria, M. T. (2021). In silico screening of natural compounds as potential inhibitors of SARS-CoV-2 main protease and spike RBD: Targets for COVID-19. Frontiers in Molecular Biosciences, 7, 599079. https://doi.org/10.3389/fmolb.2020.599079

van der Kolk, D. M., Vellenga, E., Müller, M., & de Vries, E. G. (1999). Multidrug resistance protein MRP1, glutathione, and related enzymes: Their importance in acute myeloid leukemia. Advances in Experimental Medicine and Biology, 457, 187–198. https://doi.org/10.1007/978-1-4615-4811-9_20

Wang, Y., Wu, J., Guo, W., Sun, Q., Chen, X., Zang, W., Dong, Z., & Zhao, G. (2016). α-Solanine modulates the radiosensitivity of esophageal cancer cells by inducing microRNA 138 expression. Cellular Physiology and Biochemistry, 39(3), 996–1010. https://doi.org/10.1159/000447807

Wang, N., Jiang, D., Zhou, C., & Han, X. (2023). Alpha-solanine inhibits endothelial inflammation via nuclear factor kappa B signaling pathway. Advances in Clinical and Experimental Medicine, 32(8), 909–920. https://doi.org/10.17219/acem/158781

World Health Organization. (2024). The top 10 causes of death. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death

Wu, J., Wang, L., Du, X., Sun, Q., Wang, Y., Li, M., Zang, W., Liu, K., & Zhao, G. (2018). α-Solanine enhances the chemosensitivity of esophageal cancer cells by inducing microRNA-138 expression. Oncology Reports, 39(3), 1163–1172. https://doi.org/10.3892/or.2018.6187

Yang, J., Hao, T., Sun, J., Wei, P., & Zhang, H. (2019). Long noncoding RNA GAS5 modulates α-solanine-induced radiosensitivity by negatively regulating miR-18a in human prostate cancer cells. Biomedicine & Pharmacotherapy, 112, 108656. https://doi.org/10.1016/j.biopha.2019.108656

Yi, Y. J., Jia, X. H., Wang, J. Y., Chen, J. R., Wang, H., & Li, Y. J. (2018). Solanine induced apoptosis and increased chemosensitivity to Adriamycin in T-cell acute lymphoblastic leukemia cells. Oncology Letters, 15(5), 7383–7388. https://doi.org/10.3892/ol.2018.8229

Yi, Y. J., Jia, X. H., Zhu, C., Wang, J. Y., Chen, J. R., Wang, H., & Li, Y. J. (2018). Solanine reverses multidrug resistance in human myelogenous leukemia K562/ADM cells by downregulating MRP1 expression. Oncology Letters, 15(6), 10070–10076. https://doi.org/10.3892/ol.2018.8563

Zhang, F., Yang, R., Zhang, G., Cheng, R., Bai, Y., Zhao, H., Lu, X., Li, H., Chen, S., Li, J., Wu, S., Li, P., Chen, X., Sun, Q., & Zhao, G. (2016). Anticancer function of α-solanine in lung adenocarcinoma cells by inducing microRNA-138 expression. Tumour Biology, 37(5), 6437–6446. https://doi.org/10.1007/s13277-015-4528-2

Zhang, H., Tian, F., Jiang, P., Qian, S., Dai, X., Ma, B., Wang, M., Dai, H., Sha, X., Yang, Z., Zhu, X., & Sun, X. (2021). Solasonine suppresses the proliferation of acute monocytic leukemia through the activation of the AMPK/FOXO3A axis. Frontiers in Oncology, 10, 614067. https://doi.org/10.3389/fonc.2020.614067

Zhang, N., Wu, J., Wang, Q., et al. (2023). Global burden of hematologic malignancies and evolution patterns over the past 30 years. Blood Cancer Journal, 13, 82. https://doi.org/10.1038/s41408-023-00853-3

Zhao, D., Zhao, Y., Chen, S., & Kennelly, E. J. (2021). Solanum steroidal glycoalkaloids: Structural diversity, biological activities, and biosynthesis. Natural Product Reports, 38(8). https://doi.org/10.1039/d1np00001b

Zhao, L., Wang, L., Di, S. N., Xu, Q., Ren, Q. C., Chen, S. Z., Huang, N., Jia, D., & Shen, X. F. (2018). Steroidal alkaloid solanine A from Solanum nigrum Linn. exhibits anti-inflammatory activity in lipopolysaccharide/interferon γ-activated murine macrophages and animal models of inflammation. Biomedicine & Pharmacotherapy, 105, 606–615. https://doi.org/10.1016/j.biopha.2018.06.019

Zheng, Y., Li, L., Gao, Q., Niu, B., & Wang, H. (2020). Solanine inhibits proliferation and promotes apoptosis of the human leukemia cells by targeting the miR-16/Bcl-2 axis. Journal of BUON, 25(3), 1614–1618. PMID: 32862612

Zhou, J., Wu, J., Fu, F., Yao, S., Zheng, W., Du, W., Luo, H., Jin, H., Tong, P., Wu, C., & Ruan, H. (2024). α-Solanine attenuates chondrocyte pyroptosis to improve osteoarthritis via suppressing NF-κB pathway. Journal of Cellular and Molecular Medicine, 28(4), e18132. https://doi.org/10.1111/jcmm.18132

Zhu, C., Jia, X., Yi, Y., & Li, Y. (2017). Reversal effect of solanine on multidrug-resistance of leukemia K562/ADR cells and its mechanism. Tumor, 37, 1276–1281. https://doi.org/10.3781/j.issn.1000-7431.2017.11.604

Zou, T., Gu, L., Yang, L., Wei, J., Zhao, Y., Shen, J., Li, M., Wu, X., Du, F., Chen, Y., Ye, Y., Xiao, Z., & Wu, Z. (2022). Alpha-solanine anti-tumor effects in non-small cell lung cancer through regulating the energy metabolism pathway. Recent Patents on Anti-Cancer Drug Discovery, 17(4), 396–409. https://doi.org/10.2174/1574892817666220113144635

Zupkó, I., Molnár, J., Réthy, B., Minorics, R., Frank, E., Wölfling, J., Molnár, J., Ocsovszki, I., Topcu, Z., Bitó, T., & Puskás, L. G. (2014). Anticancer and multidrug resistance-reversal effects of solanidine analogs synthetized from pregnadienolone acetate. Molecules, 19(2), 2061–2076. https://doi.org/10.3390/molecules19022061

Downloads

Published

2026-05-30

How to Cite

Alicja Szymczak, Anna Jaworowicz, Joanna Piasecka, Bartosz Gołembiewski, Grzegorz Mulski, Martyna Manicka, Michał Baranowicz, Weronika Mazurkiewicz, Zuzanna Borecka, & Agnieszka Marta Sobczak. (2026). STEROIDAL ALKALOIDS FROM SOLANACEAE SPECIES IN HEMATOLOGICAL MALIGNANCIES: MECHANISMS AND THERAPEUTIC POTENTIAL. International Journal of Innovative Technologies in Social Science, 3(2(50). https://doi.org/10.31435/ijitss.2(50).2026.5084