Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jan 5;16(2):244.
doi: 10.3390/cancers16020244.

Harnessing Sulforaphane Potential as a Chemosensitizing Agent: A Comprehensive Review

Bethsebie Lalduhsaki Sailo  1 , Le Liu  2 , Suravi Chauhan  1 , Sosmitha Girisa  1 , Mangala Hegde  1 , Liping Liang  3 , Mohammed S Alqahtani  4 , Mohamed Abbas  5 , Gautam Sethi  6 , Ajaikumar B Kunnumakkara  1
Affiliations
Review

Harnessing Sulforaphane Potential as a Chemosensitizing Agent: A Comprehensive Review

Bethsebie Lalduhsaki Sailo et al. Cancers (Basel). .

Abstract

Recent advances in oncological research have highlighted the potential of naturally derived compounds in cancer prevention and treatment. Notably, sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables including broccoli and cabbage, has exhibited potent chemosensitizing capabilities across diverse cancer types of bone, brain, breast, lung, skin, etc. Chemosensitization refers to the enhancement of cancer cell sensitivity to chemotherapy agents, counteracting the chemoresistance often developed by tumor cells. Mechanistically, SFN orchestrates this sensitization by modulating an array of cellular signaling pathways (e.g., Akt/mTOR, NF-κB, Wnt/β-catenin), and regulating the expression and activity of pivotal genes, proteins, and enzymes (e.g., p53, p21, survivin, Bcl-2, caspases). When combined with conventional chemotherapeutic agents, SFN synergistically inhibits cancer cell proliferation, invasion, migration, and metastasis while potentiating drug-induced apoptosis. This positions SFN as a potential adjunct in cancer therapy to augment the efficacy of standard treatments. Ongoing preclinical and clinical investigations aim to further delineate the therapeutic potential of SFN in oncology. This review illuminates the multifaceted role of this phytochemical, emphasizing its potential to enhance the therapeutic efficacy of anti-cancer agents, suggesting its prospective contributions to cancer chemosensitization and management.

Keywords: cancer; chemoresistance; chemosensitization; phytochemicals; sulforaphane.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Molecular mechanism of cancer chemoresistance. Chemoresistance manifests through either genetic predisposition or acquired mechanisms. The predominant molecular determinants underlying resistance to cancer therapeutics encompass (1) Altered expression of transport proteins governing drug absorption, resulting in diminished absorption rates and subsequent chemoresistance, (2) Anomalous expression of the ABC family proteins, leading to the efflux of drugs from the cellular milieu, thereby reducing intracellular drug concentrations to levels insufficient for drug sensitivity, (3) Perturbations in targeted signaling pathways, (4) Tumor microenvironmental factors including hypoxia, low pH, elevated cytokine levels, and heterogeneity, (5) Metabolic reprogramming of tumor cells, (6) Induction of epithelial-mesenchymal transition (EMT) properties conferring resistance to chemotherapy and radiotherapy, (7) Prompt repair of DNA damage inflicted by chemotherapy and radiotherapy, closely linked to the acquisition of chemoresistance, (8) Inhibition of cell death processes, (9) Activation of autophagy, (10) Augmented signaling pathways associated with survival, indicating an imbalance between apoptosis and cell growth, modulated by major gene families such as p53 and Bcl, (11) Drug inactivation, wherein detoxification-related proteins deactivate drugs within cells, culminating in the acquisition of chemoresistance.
Figure 2
Figure 2
Sources of SFN and its broad spectrum against a wide range of diseases. The different types of cruciferous vegetables are rich in glucosinolates (GLS) like broccoli, kale, cabbage, etc. Under the action of myrosinases present in the gut, GLS becomes converted into sulforaphane SFN, which targets a wide range of diseases like neurogenerative disorders, cancer, autoimmune disorders, cardiovascular diseases, inflammation, metabolic diseases like diabetes, non-alcoholic fatty liver, etc.
Figure 3
Figure 3
Anti-cancer activities of SFN—Numerous investigations have elucidated the anti-cancer properties of SFN both in vitro and in vivo. SFN elicits anti-cancer effects by inducing DNA damage and ROS production, promoting cell cycle arrest, mitochondrial membrane depolarization, and apoptosis, while concurrently inhibiting proliferation, EMT, angiogenesis, tumor weight, and other related processes.
Figure 4
Figure 4
Molecular targets of SFN—SFN exerts its anti-cancer effects by modulating key molecular targets, including caspases, Bid, Bax, p53, Nrf2, p21, NF-κB, cyclin D1, E-cadherin, VEGF, and Bcl-2. This modulation intricately regulates diverse processes in cancer.
Figure 5
Figure 5
Chemosensitization action of SFN in combination therapy against various cancers—The general overview of combination therapy used against different types of cancers. The treatment uses a combination of SFN, conventional anti-cancer agents, and/or conventional therapies like chemotherapy to achieve chemosensitization.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Saini A., Kumar M., Bhatt S., Saini V., Malik A. Cancer causes and treatments. Int. J. Pharm. Sci. Res. 2020;11:3121–3134.
    1. Khatoon E., Banik K., Harsha C., Sailo B.L., Thakur K.K., Khwairakpam A.D., Vikkurthi R., Devi T.B., Gupta S.C., Kunnumakkara A.B. Phytochemicals in cancer cell chemosensitization: Current knowledge and future perspectives. Semin. Cancer Biol. 2022;80:306–339. doi: 10.1016/j.semcancer.2020.06.014. - DOI - PubMed
    1. Ranjan A., Ramachandran S., Gupta N., Kaushik I., Wright S., Srivastava S., Das H., Srivastava S., Prasad S., Srivastava S.K. Role of Phytochemicals in Cancer Prevention. Int. J. Mol. Sci. 2019;20:4981. doi: 10.3390/ijms20204981. - DOI - PMC - PubMed
    1. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell. 2000;100:57–70. doi: 10.1016/S0092-8674(00)81683-9. - DOI - PubMed
    1. Hanahan D., Weinberg R.A. The hallmarks of cancer: The next generation. Cell. 2011;144:664–674. doi: 10.1016/j.cell.2011.02.013. - DOI - PubMed

Grants and funding

This work was supported by BT/556/NE/U-Excel/2016 grant awarded to Ajaikumar B. Kunnumakkara by Department of Biotechnology (DBT), Government of India. Mohammed S. Alqahtani and Mohamed Abbas extend their appreciation to the Deanship of Scientific Research at King Khalid University (KKU) for funding this research through the Research Group Program Under the Grant Number:(R.G.P.2/555/44). This study was supported by grants from the National Natural Science Foundation of China (NO. 82200612).