Cancer cell signaling pathways targeted by spice-derived nutraceuticals
Open accessAbstract
Extensive research within the last half a century has revealed that cancer is caused by dysregulation of as many as 500 different gene products. Most natural products target multiple gene products and thus are ideally suited for prevention and treatment of various chronic diseases, including cancer. Dietary agents such as spices have been used extensively in the Eastern world for a variety of ailments for millennia, and five centuries ago they took a golden journey to the Western world. Various spice-derived nutraceuticals, including 1'-acetoxychavicol acetate, anethole, capsaicin, cardamonin, curcumin, dibenzoylmethane, diosgenin, eugenol, gambogic acid, gingerol, thymoquinone, ursolic acid, xanthohumol, and zerumbone derived from galangal, anise, red chili, black cardamom, turmeric, licorice, fenugreek, clove, kokum, ginger, black cumin, rosemary, hop, and pinecone ginger, respectively, are the focus of this review. The modulation of various transcription factors, growth factors, protein kinases, and inflammatory mediators by these spice-derived nutraceuticals are described. The anticancer potential through the modulation of various targets is also the subject of this review. Although they have always been used to improve taste and color and as a preservative, they are now also used for prevention and treatment of a wide variety of chronic inflammatory diseases, including cancer.
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Eugenol inhibits tumor proliferation and formation, increases reactive oxygen species (ROS), generates apoptosis, and has a genotoxic effect in different cancer cells.
“Eugenol inhibits tumor proliferation and formation, increases reactive oxygen species (ROS), generates apoptosis, and has a genotoxic effect in different cancer cells [23,29,30,31].”
From Clove essential oil (Syzygium aromaticum L. Myrtaceae): Extraction, chemical composition, food applications, and essential bioactivity for human health (2021) · cites this paper as [29]
The Proinflammatory Mediators section (page unavailable) reports that eugenol inhibited proliferation of HT-29 cancer cells. A cited study listed in the References (page unavailable) describes prevention of mouse skin carcinogenesis and induction of apoptosis, but the copy does not establish these effects across different cancer cells. It also does not support the claimed increase in ROS or genotoxic effect. (LLM, conf=0.87)
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Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases
Kunnumakkara, A. B., Bordoloi, D., Padmavathi, G., Monisha, J., Roy, N. K., Prasad, S., & Aggarwal, B. B. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13621 · Cited by 1,068 · see citing works
Self-citationThe role and place of medicinal plants in the strategies for disease prevention
Sofowora, A., Ogunbodede, E. O., & Onayade, A. A. (2013) · African Journal of Traditional Complementary and Alternative Medicines · doi:10.4314/ajtcam.v10i5.2 · Cited by 1,047 · see citing works
Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors
Siveen, K. S., Sikka, S., Surana, R., Dai, X., Zhang, J., Kumar, A. P., Tan, B. K. H., Sethi, G., & Bishayee, A. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2013.12.005 · Cited by 637 · see citing works
Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?
He, Y., Yue, Y., Zheng, X., Zhang, K., Chen, S., & Du, Z. (2015) · Molecules · doi:10.3390/molecules20059183 · Cited by 611 · see citing works
Pulido‐Moran, M., Moreno‐Fernández, J., Ramírez-Tortosa, C. L., & Ramírez-Tortosa, M. C. (2016) · Molecules · doi:10.3390/molecules21030264 · Cited by 555 · see citing works
Haro-González, J. N., Castillo-Herrera, G. A., Martínez-Velázquez, M., & Espinosa-Andrews, H. (2021) · Molecules · doi:10.3390/molecules26216387 · Cited by 463 · see citing works
Role of Phytochemicals in Cancer Prevention
Ranjan, A., Ramachandran, S., Gupta, N., Kaushik, I., Wright, S. E., Srivastava, S., Das, H., Srivastava, S., Prasad, S., & Srivastava, S. K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20204981 · Cited by 371 · see citing works
Self-citationChronic diseases, inflammation, and spices: how are they linked?
Kunnumakkara, A. B., Sailo, B. L., Banik, K., Harsha, C., Prasad, S., Gupta, S. C., Bharti, A. C., & Aggarwal, B. B. (2018) · Journal of Translational Medicine · doi:10.1186/s12967-018-1381-2 · Cited by 345 · see citing works
Self-citationDiosgenin: Recent Highlights on Pharmacology and Analytical Methodology
Jesus, M., Martins, A. P. J., Gallardo, E., & Silvestre, S. (2016) · Journal of Analytical Methods in Chemistry · doi:10.1155/2016/4156293 · Cited by 273 · see citing works
Healthy aging diets other than the Mediterranean: A focus on the Okinawan diet
Willcox, D. C., Scapagnini, G., & Willcox, B. J. (2014) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2014.01.002 · Cited by 273 · see citing works
Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review
Sethi, G., Shanmugam, M. K., Warrier, S. R., Mérarchi, M., Arfuso, F., Kumar, A. P., & Bishayee, A. (2018) · Nutrients · doi:10.3390/nu10050645 · Cited by 254 · see citing works
Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer
Tan, B. L., & Norhaizan, M. E. (2019) · Molecules · doi:10.3390/molecules24142527 · Cited by 246 · see citing works
Is curcumin bioavailability a problem in humans: lessons from clinical trials
Kunnumakkara, A. B., Harsha, C., Banik, K., Vikkurthi, R., Sailo, B. L., Bordoloi, D., Gupta, S. C., & Aggarwal, B. B. (2019) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2019.1650914 · Cited by 211 · see citing works
Self-citationYaffe, P. B., Coombs, M. R. P., Doucette, C. D., Walsh, M. J., & Hoskin, D. W. (2014) · Molecular Carcinogenesis · doi:10.1002/mc.22176 · Cited by 188 · see citing works
González-Reyes, S., Guzmán‐Beltrán, S., Medina‐Campos, O. N., & Pedraza‐Chaverrí, J. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/801418 · Cited by 180 · see citing works
Potential of Zerumbone as an Anti-Cancer Agent
Girisa, S., Shabnam, B., Monisha, J., Fan, L., Halim, C. E., Arfuso, F., Ahn, K. S., Sethi, G., & Kunnumakkara, A. B. (2019) · Molecules · doi:10.3390/molecules24040734 · Cited by 161 · see citing works
Spices: The Savory and Beneficial Science of Pungency
Nilius, B., & Appendino, G. (2013) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2013_11 · Cited by 160 · see citing works
Beneficial Effects of Spices in Food Preservation and Safety
Gottardi, D., Bukvički, D., Prasad, S., & Tyagi, A. K. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01394 · Cited by 165 · see citing works
Self-citationChtourou, Y., Aouey, B., Kebieche, M., & Fetoui, H. (2015) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2015.06.036 · Cited by 130 · see citing works
Chen, H., & Liu, R. H. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.7b04975 · Cited by 127 · see citing works
Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics
Hatami, E., Jaggi, M., Chauhan, S. C., & Yallapu, M. M. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188381 · Cited by 127 · see citing works
Pandey, V. K., Srivastava, S., Ashish, Dash, K. K., Singh, R., Dar, A. H., Singh, T., Farooqui, A., Shaikh, A. M., & Kovács, B. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e22437 · Cited by 124 · see citing works
Gonçalves, L. M., Valente, I. M., & Rodrigues, J. A. (2014) · Journal of Medicinal Food · doi:10.1089/jmf.2013.0061 · Cited by 122 · see citing works
Anethole and Its Role in Chronic Diseases
Aprotosoaie, A. C., Costache, I. I., & Miron, A. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-41342-6_11 · Cited by 115 · see citing works
Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies
Mostofa, A., Hossain, M. K., Basak, D., & Sayeed, M. S. B. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00295 · Cited by 115 · see citing works
Targeting oncogenic transcription factors by polyphenols: A novel approach for cancer therapy
Rajagopal, C., Lankadasari, M. B., Aranjani, J. M., & Harikumar, K. B. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2017.12.034 · Cited by 113 · see citing works
Hasanin, M. S., Hashem, A. H., El-Rashedy, A. A. E., & Kamel, S. M. (2021) · Cellulose · doi:10.1007/s10570-021-04063-7 · Cited by 109 · see citing works
Cancer Chemoprevention by Phytochemicals: Nature’s Healing Touch
Zubair, H., Azim, S., Ahmad, A., Khan, M. A., Patel, G. K., Singh, S., & Singh, A. P. (2017) · Molecules · doi:10.3390/molecules22030395 · Cited by 105 · see citing works
COVID-19, cytokines, inflammation, and spices: How are they related?
Kunnumakkara, A. B., Rana, V., Parama, D., Banik, K., Girisa, S., Henamayee, S., Thakur, K. K., Dutta, U., Garodia, P., Gupta, S. C., et al. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119201 · Cited by 105 · see citing works
Self-citationCurcumin: a therapeutic strategy in cancers by inhibiting the canonical WNT/β-catenin pathway
Vallée, A., Lecarpentier, Y., & Vallée, J.-N. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1320-y · Cited by 104 · see citing works
Nosrati, N., Bakovic, M., & Paliyath, G. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102050 · Cited by 88 · see citing works
Margina, D. M., Ungurianu, A., Purdel, C. N., Nițulescu, G. M., Tsoukalas, D., Sarandi, E., Thanasoula, M., Burykina, T. I., Tekos, F., Djordjević, A. B., et al. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111558 · Cited by 86 · see citing works
Singh, A. K., Sharma, N., Ghosh, M., Park, Y. H., & Jeong, D. K. (2016) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2015.1129310 · Cited by 82 · see citing works
Study of phytochemical, anti-microbial, anti-oxidant, and anti-cancer properties of Allium wallichii
Bhandari, J., Muhammad, B. T., Thapa, P., & Shrestha, B. G. (2017) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-017-1622-6 · Cited by 82 · see citing works
The good and bad of antioxidant foods: An immunological perspective
Gostner, J. M., Becker, K., Ueberall, F., & Fuchs, D. (2015) · Food and Chemical Toxicology · doi:10.1016/j.fct.2015.02.012 · Cited by 80 · see citing works
Hajizadeh, M. R., Parvaz, N., Barani, M., Khoshdel, A., Fahmidehkar, M. A., Mahmoodi, M., & Torkzadeh‐Mahani, M. (2019) · DARU Journal of Pharmaceutical Sciences · doi:10.1007/s40199-019-00277-0 · Cited by 74 · see citing works
Curcumin’s Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions
Zhai, K., Brockmueller, A., Kubatka, P., Shakibaei, M., & Büsselberg, D. (2020) · Biomolecules · doi:10.3390/biom10111469 · Cited by 74 · see citing works
Regulation of cell signaling pathways by dietary agents for cancer prevention and treatment
Pandey, M. K., Gupta, S. C., Nabavizadeh, A., & Aggarwal, B. B. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.07.002 · Cited by 72 · see citing works
Self-citationDialdehyde cellulose as a niche material for versatile applications: an overview
Dalei, G., Das, S., & Pradhan, M. (2022) · Cellulose · doi:10.1007/s10570-022-04619-1 · Cited by 68 · see citing works
Paranjpe, R., Gundala, S. R., Narayana, L., Sagwal, A., Asif, G., Pandey, A., & Aneja, R. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt066 · Cited by 67 · see citing works
Kim, S. O., & Kim, M.-R. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/761852 · Cited by 66 · see citing works
Diet-Derived Phytochemicals Targeting Colon Cancer Stem Cells and Microbiota in Colorectal Cancer
Ganesan, K., Jayachandran, M., & Xu, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21113976 · Cited by 65 · see citing works
Gupta, D. D., Mishra, S., Verma, S. S., Shekher, A., Rai, V., Awasthee, N., Das, T. J., Paul, D., Das, S. K., Tag, H., et al. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.113842 · Cited by 64 · see citing works
Anticancer potential of Trigonella foenum graecum: Cellular and molecular targets
Bairi, K. E., Ouzir, M., Najda, A., & Khalki, L. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.03.071 · Cited by 63 · see citing works
The Toxicity and Pathology of Selected Dietary Herbal Medicines
Dunnick, J. K., & Nyska, A. (2012) · Toxicologic Pathology · doi:10.1177/0192623312466451 · Cited by 61 · see citing works
Hackler, L., Ózsvári, B., Gyuris, M., Sipos, P., Fábián, G., Molnár, E., Marton, A., Faragó, N., Mihály, J., Nagy, L. I., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149832 · Cited by 60 · see citing works
Fakhri, S., Moradi, S. Z., Yarmohammadi, A., Narimani, F., Wallace, C. E., & Bishayee, A. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.834072 · Cited by 59 · see citing works
Singh, B. N., Singh, H., Singh, A., Naqvi, A., & Singh, B. R. (2014) · Cancer Metastasis Review · doi:10.1007/s10555-013-9457-1 · Cited by 61 · see citing works
Anticancer Effects of Herbal Medicine Compounds and Novel Formulations: a Literature Review
Abdulridha, M. K., AL-Marzoqi, A. H., Al‐Awsi, G. R. L., Mubarak, S. M. H., Heidarifard, M., & Ghasemian, A. (2020) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-020-00385-0 · Cited by 58 · see citing works
Hseu, Y., Chang, C.-T., Gowrisankar, Y. V., Chen, X., Lin, H., Yen, H., & Yang, H. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/4098674 · Cited by 54 · see citing works
Chan, M., Liang, J., Hsu, L., Chang, W., Lee, S., & Guh, J. (2015) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-015-1152-z · Cited by 53 · see citing works
Thomas, S., Dhanya, B. P., Arun, K. B., Sini, S., Dan, M., Vasu, R. K., & Nisha, P. (2017) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.7b04472 · Cited by 51 · see citing works
Alam, S., Mohammad, T., Padder, R. A., Hassan, M. I., & Husain, M. (2021) · Journal of Cellular Biochemistry · doi:10.1002/jcb.30162 · Cited by 50 · see citing works
Wirries, A., Schubert, A., Zimmermann, R., Jabari, S., Ruchholtz, S., & El‐Najjar, N. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2012.12.033 · Cited by 50 · see citing works
Polyphenolic molecules targeting STAT3 pathway for the treatment of cancer
Aziz, M. A., Sarwar, M. S., Akter, T., Uddin, M. S., Xun, S., Zhu, Y., Islam, M. S., & Hongjie, Z. (2021) · Life Sciences · doi:10.1016/j.lfs.2020.118999 · Cited by 48 · see citing works
Fenugreek extract as an inducer of cellular death via autophagy in human T lymphoma Jurkat cells
Al‐Daghri, N. M., Alokail, M. S., Alkharfy, K. M., Mohammed, A. K., Abd-Alrahman, S. H., Yakout, S. M., Amer, O. E., & Krishnaswamy, S. (2012) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-12-202 · Cited by 48 · see citing works
Chemistry and Biochemistry of Terpenoids fromCurcumaand Related Species
Afzal, A., Oriqat, G., Khan, M. A., Jose, J., & Afzal, M. (2013) · Journal of Biologically Active Products from Nature · doi:10.1080/22311866.2013.782757 · Cited by 47 · see citing works
Antiangiogenic Effects and Mechanisms of trans-Ethyl p-Methoxycinnamate from Kaempferia galanga L.
He, Z., Yue, G. G., Lau, C. B., Ge, W., & But, P. P. (2012) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf304169j · Cited by 45 · see citing works
Cytotoxic Half-Sandwich Rh(III) and Ir(III) β-Diketonates
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Curcumin Reduces Cytotoxicity of 5-Fluorouracil Treatment in Human Breast Cancer Cells
Ferguson, J. E., & Orlando, R. A. (2014) · Journal of Medicinal Food · doi:10.1089/jmf.2013.0086 · Cited by 43 · see citing works
Molecular Targets of Naturopathy in Cancer Research: Bridge to Modern Medicine
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Therapeutic potentials of natural compounds acting on cyclic nucleotide phosphodiesterase families
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Capsaicin inhibits cell proliferation by cytochrome c release in gastric cancer cells
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Bioactives from culinary spices and herbs: a review
Embuscado, M. E. (2019) · Journal of Food Bioactives · doi:10.31665/jfb.2019.6186 · Cited by 35 · see citing works
Stimulating the proliferation, migration and lamellipodia of Schwann cells using low-dose curcumin
Velasquez, J. T., Nazareth, L., Quinn, R. J., Ekberg, J. A. K., & John, J. A. S. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.02.073 · Cited by 35 · see citing works
Kumar, A., Hegde, M., Parama, D., & Kunnumakkara, A. B. (2022) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.2023045587 · Cited by 35 · see citing works
The Healing Effects of Spices in Chronic Diseases
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Self-citationKiss, R., Pesti‐Asbóth, G., Szarvas, M. M., Stündl, L., Cziáky, Z., Hegedűs, C., Kovács, D. K., Badale, A., Máthé, E., Szilvássy, Z., et al. (2019) · BioMed Research International · doi:10.1155/2019/7213913 · Cited by 34 · see citing works
The treatment role of Cyperus rotundus L. to triple-negative breast cancer cells
Wang, F., Song, X., Ma, S., Liu, C., Sun, X., Wang, X., Liu, Z., Liang, D., & Yu, Z. (2019) · Bioscience Reports · doi:10.1042/bsr20190502 · Cited by 34 · see citing works
Cardamonin Attenuates Experimental Colitis and Associated Colorectal Cancer
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Zhang, L., Gu, B., & Wang, Y. (2020) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2020.108938 · Cited by 32 · see citing works
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Chemopreventive Potential of Dietary Nanonutraceuticals for Prostate Cancer: An Extensive Review
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Exploring the Therapeutic Potential of Bioactive Compounds from Plant Sources
Chintada, V., & Golla, N. (2025) · Sustainable landscape planning and natural resources management · doi:10.1007/978-3-031-76859-0_15 · Cited by 25 · see citing works
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Curcumin: A Potential Weapon in the Prevention and Treatment of Head and Neck Cancer
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Effect of selected spices on chemical and sensory markers in fortified rye‐buckwheat cakes
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Target Identification and Polypharmacology of Nutraceuticals
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Biocompatible polymeric nanoparticles as carriers for anticancer phytochemicals
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- Authors
- Sung, B., Prasad, S., Yadav, V. R., & Aggarwal, B. B.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Venue
- Nutrition and Cancer
- Publisher
- Informa UK Limited
- Published
- 2012-02
- Volume
- 64
- Issue
- 2
- Pages
- 173-197
- ISSN
- 0163-5581 (ISSN-L)
- 1532-7914
- PMC
- PMC3645308
- OpenAlex
- W2035997417
- Cited by
- 204
- References
- 324
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 11 · 2023: 10 · 2022: 18 · 2021: 28 · 2020: 11 · 2019: 17 · 2018: 9 · 2017: 15 · 2016: 18 · 2015: 14 · 2014: 13 · 2013: 20 · 2012: 7
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nutrition and Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA-16672, P01CA124787, CA-124787-01A2, P30CA016672)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Medicinal Plant Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioactive natural compounds
- Keywords
- anticancer agents, curcumin, gingerol, xanthohumol, eugenol, thymoquinone, capsaicin, anethole, cardamonin, gambogic acid, ursolic acid, dibenzoylmethane, diosgenin, Nigella sativa, licorice, turmeric, Syzygium aromaticum, black cardamom, galangal, red chili, Rosmarinus officinalis, Humulus lupulus, fenugreek, kokum, transcription factors, protein kinases, growth factors, inflammatory mediators, cancer prevention
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, Humans, Phytotherapy, Neoplasms, Protein Kinases, Transcription Factors, Signal Transduction, NF-kappa B, Spices, Receptors, Growth Factor, Inflammation Mediators, Dietary Supplements, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Protein Kinase Inhibitors
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