Anticancer Activity of Allium cepa through the Inactivation of NF-κB Pathway: A Literature-based Study

Sharmita Ghosh Situ; Md. Sakib Al  Hasan; Emon  Mia; Md. Nasimul Haque  Shipon; Md Faisal  Amin; Asmaul Husna  Bristy; Yasin  Emon

doi:10.71193/jcid.20250004

Authors

Sharmita Ghosh Situ Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh Author https://orcid.org/0009-0005-4212-7821
Md. Sakib Al Hasan Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh Author https://orcid.org/0009-0004-7560-4041
Emon Mia Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh Author https://orcid.org/0009-0007-7390-056X
Md. Nasimul Haque Shipon Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh Author https://orcid.org/0009-0001-7693-303X
Md Faisal Amin School of Integrative Biological and Chemical Sciences, The University of Texas Rio Grande Valley, USA Author https://orcid.org/0009-0009-9274-1335
Asmaul Husna Bristy Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh Author https://orcid.org/0009-0007-6921-0291
Yasin Emon Department of Pharmacy, Islamic University, Kushtia 7003, Bangladesh Author https://orcid.org/0000-0002-0033-7346

DOI:

https://doi.org/10.71193/jcid.20250004

Keywords:

Allium cepa, Cancer, NF-κB inhibitor, Phytochemicals, Quercetin

Abstract

Allium cepa (onion) is a bulbous herb renowned for its diverse health benefits. This study aims to summarize the anticancer potential of A. cepa through the inactivation of the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reviewing experimental findings across various cancer models. A thorough examination of the literature was carried out using databases like Google Scholar, PubMed, Web of Science, and ScienceDirect. The findings revealed that phytochemicals such as stigmasterol, fisetin, quercetin, isorhamnetin, morin, kaempferol, luteolin, β-carotene, and β-sitosterol exhibit strong anticancer properties against various cancers, including breast, bladder, colon, colorectal, cervical, lung, liver, oral, pancreatic, and skin cancer, as supported by both in vivo and in vitro studies. These phytochemicals primarily exert their anticancer effects by blocking the NF-κB signaling pathway. However, further clinical research is needed to investigate its in vivo and in vitro study to determine its safety and efficacy in cancer treatment, with a focus on optimizing its therapeutic nature.

Downloads

Download data is not yet available.

Author Biographies

Sharmita Ghosh Situ, Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh

Sharmita Ghosh Situ is a M. Pharm. student in Pharmacy at GSTU, Gopalganj 8100, Bangladesh. She is also working as an active researcher at BioLuster Research Center Ltd., Dhaka, Bangladesh. She is mainly interested in cancer, neurology, in silico studies, and natural compounds.
Md. Sakib Al Hasan, Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh

Md. Sakib Al Hasan is a B. Pharm. student in Pharmacy at GSTU, Gopalganj 8100, Bangladesh. He is also working as Financial and Documentation Officer at BioLuster Research Center Ltd., Dhaka, Bangladesh. He is mainly interested in cancer, neurology, computational drug design, in silico studies, vaccine designing and natural compounds.

References

Afroze, N., Pramodh, S., Almutary, A. G., Rizvi, T. A., Rais, N., Raina, R., ... & Hussain, A. (2022). Kaempferol regresses carcinogenesis through a molecular cross talk involved in proliferation, apoptosis and inflammation on human cervical cancer cells, HeLa. Applied Sciences, 12(6), 3155. https://doi.org/10.3390/app12063155 DOI: https://doi.org/10.3390/app12063155

Aktar, A., Bhuia, S., Chowdhury, R., Ferdous, J., Khatun, M., Hasan, S. A., Mia, E., Hasan, R., & Islam, M. T. (2024). An Insight of Plant Source, Toxicological Profile, and Pharmacological Activities of Iridoid Loganic Acid: A ComprehensiveReview. Chemistry & biodiversity, 21(12), e202400874. https://doi.org/10.1002/cbdv.202400874 DOI: https://doi.org/10.1002/cbdv.202400874

Al Hasan, M. S., Bhuia, M. S., Chowdhury, R., Shadin, M., Mia, E., Yana, N. T., ... & Islam, M. T. (2025). Anticancer activity of Jasminum sambac and its bioactive phytochemicals against the PI3K-AKT-mTOR pathway: A literature-based in silico study. South African Journal of Botany, 180, 431-443. https://doi.org/10.1016/j.sajb.2025.03.004 DOI: https://doi.org/10.1016/j.sajb.2025.03.004

Al Hasan, M. S., Mia, E., Yana, N. T., Rakib, I. H., Bhuia, M. S., Chowdhury, R., ... & Islam, M. T. (2024). Allium cepa bioactive phytochemicals as potent ALK (Anaplastic lymphoma kinase) inhibitors and therapeutic agents against non-small cell lung cancer (NSCLC): A computational study. Pharmacological Research-Natural Products, 5, 100124. https://doi.org/10.1016/j.prenap.2024.100124 DOI: https://doi.org/10.1016/j.prenap.2024.100124

Alpsoy, S., Aktas, C., Uygur, R., Topcu, B., Kanter, M., Erboga, M., Karakaya, O., & Gedikbasi, A. (2013). Antioxidant and anti-apoptotic effects of onion (Allium cepa) extract on doxorubicin-induced cardiotoxicity in rats. Journal of applied toxicology: JAT, 33(3), 202–208. https://doi.org/10.1002/jat.1738. DOI: https://doi.org/10.1002/jat.1738

Askari, G., Ghiasvand, R., Feizi, A., Ghanadian, S. M., & Karimian, J. (2012). The effect of quercetin supplementation on selected markers of inflammation and oxidative stress. Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences, 17(7), 637.

Ayaz, M., Nawaz, A., Ahmad, S., Mosa, O. F., Eisa Hamdoon, A. A., Khalifa, M. A., ... & Ananda Murthy, H. C. (2022). Underlying anticancer mechanisms and synergistic combinations of phytochemicals with cancer chemotherapeutics: potential benefits and risks. Journal of Food Quality, 2022(1), 1189034. https://doi.org/10.1155/2022/1189034 DOI: https://doi.org/10.1155/2022/1189034

Bithi, S. A., Al Hasan, M. S., Bhuia, M. S., Mia, E., Yana, N. T., Hasan, A. M. W., Uddin, M. B., Sayeed, M. A., Emon, Y., Hasan, R., Chowdhury, R., & Islam, M. T. (2025). Botanical sources, biopharmaceutical profile, anticancer effects with mechanistic insight, toxicological and clinical evidence of prunetin: a literature review. Medical oncology (Northwood, London, England), 42(4), 87. https://doi.org/10.1007/s12032-025-02646-z DOI: https://doi.org/10.1007/s12032-025-02646-z

Brown, M., Cohen, J., Arun, P., Chen, Z., & Van Waes, C. (2008). NF-kappaB in carcinoma therapy and prevention. Expert opinion on therapeutic targets, 12(9), 1109–1122. https://doi.org/10.1517/14728222.12.9.1109 DOI: https://doi.org/10.1517/14728222.12.9.1109

Cao, Z. Q., Wang, X. X., Lu, L., Xu, J. W., Li, X. B., Zhang, G. R., Ma, Z. J., Shi, A. C., Wang, Y., & Song, Y. J. (2019). β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling. Frontiers in pharmacology, 9, 1525. https://doi.org/10.3389/fphar.2018.01525 DOI: https://doi.org/10.3389/fphar.2018.01525

Chauhan, A., Islam, A. U., Prakash, H., & Singh, S. (2022). Phytochemicals targeting NF-κB signaling: Potential anti-cancer interventions. Journal of pharmaceutical analysis, 12(3), 394–405. https://doi.org/10.1016/j.jpha.2021.07.002 DOI: https://doi.org/10.1016/j.jpha.2021.07.002

Downing, N. S., Aminawung, J. A., Shah, N. D., Krumholz, H. M., & Ross, J. S. (2014). Clinical trial evidence supporting FDA approval of novel therapeutic agents, 2005-2012. JAMA, 311(4), 368–377. https://doi.org/10.1001/jama.2013.282034 DOI: https://doi.org/10.1001/jama.2013.282034

Duan, R., Liang, X., Chai, B., Zhou, Y., Du, H., Suo, Y., Chen, Z., Li, Q., & Huang, X. (2020). Isorhamnetin Induces Melanoma Cell Apoptosis via the PI3K/Akt and NF-κB Pathways. BioMed research international, 2020, 1057943. https://doi.org/10.1155/2020/1057943 DOI: https://doi.org/10.1155/2020/1057943

Fadholly, A., Ansori, A. N., Jayanti, S., Proboningrat, A., Kusala, M. K., Putri, N., ... & Sudjarwo, S. A. (2019). Cytotoxic effect of Allium cepa L. extract on human colon cancer (WiDr) cells: in vitro study. Research Journal of Pharmacy and Technology, 12(7), 3483-3486. DOI: https://doi.org/10.5958/0974-360X.2019.00591.2

Farsad-Naeimi, A. Alizadeh, M., Esfahani, A., & Darvish Aminabad, E., (2018). Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients. Food & function, 9(4), 2025–2031. https://doi.org/10.1039/c7fo01898c DOI: https://doi.org/10.1039/C7FO01898C

Fuchs O. (2010). Transcription factor NF-κB inhibitors as single therapeutic agents or in combination with classical chemotherapeutic agents for the treatment of hematologic malignancies. Current molecular pharmacology, 3(3), 98–122. https://doi.org/10.2174/1874467211003030098 DOI: https://doi.org/10.2174/1874467211003030098

Han, M., Song, Y., & Zhang, X. (2016). Quercetin Suppresses the Migration and Invasion in Human Colon Cancer Caco-2 Cells Through Regulating Toll-like Receptor 4/Nuclear Factor-kappa B Pathway. Pharmacognosy magazine, 12(Suppl 2), S237–S244. https://doi.org/10.4103/0973-1296.182154 DOI: https://doi.org/10.4103/0973-1296.182154

Hasan, A. M. W., Al Hasan, M. S., Mizan, M., Miah, M. S., Uddin, M. B., Mia, E., ... & Islam, M. T. (2025). Quercetin promises anticancer activity through PI3K-AKT-mTOR Pathway: a literature review. Pharmacological Research-Natural Products, 100206. https://doi.org/10.1016/j.prenap.2025.100206 DOI: https://doi.org/10.1016/j.prenap.2025.100206

Jaramillo, S., Lopez, S., Varela, L. M., Rodriguez-Arcos, R., Jimenez, A., Abia, R., Guillen, R., & Muriana, F. J. (2010). The flavonol isorhamnetin exhibits cytotoxic effects on human colon cancer cells. Journal of agricultural and food chemistry, 58(20), 10869–10875. https://doi.org/10.1021/jf102669p DOI: https://doi.org/10.1021/jf102669p

Jini, D., & Sharmila, S. J. M. T. P. (2020). Green synthesis of silver nanoparticles from Allium cepa and it’s in vitro antidiabetic activity. Materials Today: Proceedings, 22, 432-438. https://doi.org/10.1016/j.matpr.2019.07.672 DOI: https://doi.org/10.1016/j.matpr.2019.07.672

Kang, B. K., Kim, K. B. W. R., Ahn, N. K., Choi, Y. U., Kim, M. J., Bark, S. W., ... & Ahn, D. H. (2015). Anti-inflammatory effect of onion (Allium cepa) peel hot water extract in vitro and in vivo. KSBB Journal, 30(4), 148-154. https://doi.org/10.7841/ksbbj.2015.30.4.148 DOI: https://doi.org/10.7841/ksbbj.2015.30.4.148

Kang, M. J., Ryu, B. K., Lee, M. G., Han, J., Lee, J. H., Ha, T. K., Byun, D. S., Chae, K. S., Lee, B. H., Chun, H. S., Lee, K. Y., Kim, H. J., & Chi, S. G. (2008). NF-kappaB activates transcription of the RNA-binding factor HuR, via PI3K-AKT signaling, to promote gastric tumorigenesis. Gastroenterology, 135(6), 2030–2042.e20423. https://doi.org/10.1053/j.gastro.2008.08.009 DOI: https://doi.org/10.1053/j.gastro.2008.08.009

Kavalappa, Y.P., et al., β-carotene isolated from the marine red alga, Gracillaria sp. potently attenuates the growth of human hepatocellular carcinoma (HepG2) cells by modulating multiple molecular pathways. 2019. 52: p. 165-176. https://doi.org/10.1016/j.jff.2018.11.015 DOI: https://doi.org/10.1016/j.jff.2018.11.015

Kim, H. J., Hawke, N., & Baldwin, A. S. (2006). NF-kappaB and IKK as therapeutic targets in cancer. Cell death and differentiation, 13(5), 738–747. https://doi.org/10.1038/sj.cdd.4401877 DOI: https://doi.org/10.1038/sj.cdd.4401877

Kumar, K. E., Harsha, K. N., & Sudheer, V. (2013). In vitro antioxidant activity and in vivo hepatoprotective activity of aqueous extract of Allium cepa bulb in ethanol induced liver damage in Wistar rats. Food Science and Human Wellness, 2(3-4), 132-138. https://doi.org/10.1016/j.fshw.2013.10.001 DOI: https://doi.org/10.1016/j.fshw.2013.10.001

Lai, W. W., Hsu, S. C., Chueh, F. S., Chen, Y. Y., Yang, J. S., Lin, J. P., Lien, J. C., Tsai, C. H., & Chung, J. G. (2013). Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-κB and matrix metalloproteinase-2/-9 signaling pathways. Anticancer research, 33(5), 1941–1950.

Lee, H. J., Seo, H. S., Ryu, J., Yoon, Y. P., Park, S. H., & Lee, C. J. (2015). Luteolin inhibited the gene expression, production and secretion of MUC5AC mucin via regulation of nuclear factor kappa B signaling pathway in human airway epithelial cells. Pulmonary pharmacology & therapeutics, 31, 117–122. https://doi.org/10.1016/j.pupt.2014.09.008 DOI: https://doi.org/10.1016/j.pupt.2014.09.008

Li, J., Cheng, Y., Qu, W., Sun, Y., Wang, Z., Wang, H., & Tian, B. (2011). Fisetin, a dietary flavonoid, induces cell cycle arrest and apoptosis through activation of p53 and inhibition of NF-kappa B pathways in bladder cancer cells. Basic & clinical pharmacology & toxicology, 108(2), 84–93. https://doi.org/10.1111/j.1742-7843.2010.00613.x DOI: https://doi.org/10.1111/j.1742-7843.2010.00613.x

Luo, J. L., Kamata, H., & Karin, M. (2005). IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy. The Journal of clinical investigation, 115(10), 2625–2632. https://doi.org/10.1172/JCI26322 DOI: https://doi.org/10.1172/JCI26322

Manoharan, S., Rejitharaji, T., M Prabhakar, M., Manimaran, A., & B Singh, R. (2014). Modulating Effect of Ferulic Acid on NF-kB, COX-2 and VEGF Expression Pattern During 7, 12-Dimethylbenz (a) anthracene Induced Oral Carcinogenesis. The Open Nutraceuticals Journal, 7(1). DOI: https://doi.org/10.2174/1876396001407010033

Marefati, N., Ghorani, V., Shakeri, F., Boskabady, M., Kianian, F., Rezaee, R., & Boskabady, M. H. (2021). A review of anti-inflammatory, antioxidant, and immunomodulatory effects of Allium cepa and its main constituents. Pharmaceutical biology, 59(1), 287–302. https://doi.org/10.1080/13880209.2021.1874028 DOI: https://doi.org/10.1080/13880209.2021.1874028

Murtaza, I., Adhami, V. M., Hafeez, B. B., Saleem, M., & Mukhtar, H. (2009). Fisetin, a natural flavonoid, targets chemoresistant human pancreatic cancer AsPC-1 cells through DR3-mediated inhibition of NF-kappaB. International journal of cancer, 125(10), 2465–2473. https://doi.org/10.1002/ijc.24628 DOI: https://doi.org/10.1002/ijc.24628

Nakanishi, C., & Toi, M. (2005). Nuclear factor-kappaB inhibitors as sensitizers to anticancer drugs. Nature reviews. Cancer, 5(4), 297–309. https://doi.org/10.1038/nrc1588 DOI: https://doi.org/10.1038/nrc1588

Omran, G., Abd-Alhaseeb, M., & HOUSSEN, M. (2024). Chemotherapeutic effect of stigmasterol in sorafenib treated breast cancer cell lines via modulation of NF-κB and ERK signaling pathways. Egyptian Journal of Chemistry, 67(3), 227-234. 10.21608/ejchem.2023.204388.7825

Pareek, S., Sagar, N. A., Sharma, S., & Kumar, V. (2017). Onion (allium cepa L.). Fruit and Vegetable Phytochemicals: Chemistry and Human Health, 2nd Edition, 1145-1162. DOI: https://doi.org/10.1002/9781119158042.ch58

Perkins N. D. (2012). The diverse and complex roles of NF-κB subunits in cancer. Nature reviews. Cancer, 12(2), 121–132. https://doi.org/10.1038/nrc3204 DOI: https://doi.org/10.1038/nrc3204

Sasaki, N., Morisaki, T., Hashizume, K., Yao, T., Tsuneyoshi, M., Noshiro, H., Nakamura, K., Yamanaka, T., Uchiyama, A., Tanaka, M., & Katano, M. (2001). Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue. Clinical cancer research: an official journal of the American Association for Cancer Research, 7(12), 4136–4142.

Sharma, K. K., Al Hasan, M. S., Rouf, R., Emon, Y., Mia, E., Hossan, R., ... & Islam, M. T. (2025). Assessment of antiemetic and modulatory activity of dihydrocoumarin on copper sulfate induced emetic chicks: An in vivo investigation. Food Chemistry Advances, 6, 100930. https://doi.org/10.1016/j.focha.2025.100930 DOI: https://doi.org/10.1016/j.focha.2025.100930

Sharma, S. H., Kumar, J. S., Chellappan, D. R., & Nagarajan, S. (2018). Molecular chemoprevention by morin - A plant flavonoid that targets nuclear factor kappa B in experimental colon cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 100, 367–373. https://doi.org/10.1016/j.biopha.2018.02.035 DOI: https://doi.org/10.1016/j.biopha.2018.02.035

Suh, Y., Afaq, F., Johnson, J. J., & Mukhtar, H. (2009). A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB-signaling pathways. Carcinogenesis, 30(2), 300–307. https://doi.org/10.1093/carcin/bgn269 DOI: https://doi.org/10.1093/carcin/bgn269

Tong, T., Wang, Y. N., Zhang, C. M., & Kang, S. G. (2021). In vitro and in vivo antihypertensive and antioxidant activities of fermented roots of Allium hookeri. Chinese herbal medicines, 13(4), 541–548. https://doi.org/10.1016/j.chmed.2021.08.003 DOI: https://doi.org/10.1016/j.chmed.2021.08.003

Ullah, H., Minno, A. D., Santarcangelo, C., Tantipongpiradet, A., Dacrema, M., Matteo, R. D., El-Seedi, H. R., Khalifa, S. A. M., Baldi, A., Rossi, A., & Daglia, M. (2022). In Vitro Bioaccessibility and Anti-Inflammatory Activity of a Chemically Characterized Allium cepa L. Extract Rich in Quercetin Derivatives Optimized by the Design of Experiments. Molecules (Basel, Switzerland), 27(24), 9065. https://doi.org/10.3390/molecules27249065 DOI: https://doi.org/10.3390/molecules27249065

Wu, L., Pu, Z., Feng, J., Li, G., Zheng, Z., & Shen, W. (2008). The ubiquitin-proteasome pathway and enhanced activity of NF-kappaB in gastric carcinoma. Journal of surgical oncology, 97(5), 439–444. https://doi.org/10.1002/jso.20952 DOI: https://doi.org/10.1002/jso.20952

Yamada, K., Naemura, A., Sawashita, N., Noguchi, Y., & Yamamoto, J. (2004). An onion variety has natural antithrombotic effect as assessed by thrombosis/thrombolysis models in rodents. Thrombosis research, 114(3), 213–220. https://doi.org/10.1016/j.thromres.2004.06.007 DOI: https://doi.org/10.1016/j.thromres.2004.06.007

Yana, N. T. Y., Shipon, M. N. H., Bristy, A. H., Safa, F. A., Hossain, M. A., & Al Hasan, M. S. (2025). Carnosic Acid as a Promising Anticancer Agent: Mechanisms of Action and Therapeutic Potential Across Multiple Cancer Types. Journal of Chemistry Insights and Discoveries, 1(01), 1-5. https://doi.org/10.71193/jcid.20250001 DOI: https://doi.org/10.71193/jcid.20250001

Zhang, X. A., Zhang, S., Yin, Q., & Zhang, J. (2015). Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway. Pharmacognosy magazine, 11(42), 404–409. https://doi.org/10.4103/0973-1296.153096 DOI: https://doi.org/10.4103/0973-1296.153096