Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor
Milad Ashrafizadeh1, Ali Zarrabi2, Sedigheh Saberifar3
1Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran.
Abstract:
Cancer therapy is a growing field, and annually, a high number of research is performed to develop novel antitumor drugs. Attempts to find new antitumor drugs continue, since cancer cells are able to acquire resistance to conventional drugs. Natural chemicals can be considered as promising candidates in the field of cancer therapy due to their multiple-targeting capability. The nobiletin (NOB) is a ubiquitous flavone isolated from Citrus fruits. The NOB has a variety of pharmacological activities, such as antidiabetes, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective. Among them, the antitumor activity of NOB has been under attention over recent years. In this review, we comprehensively describe the efficacy of NOB in cancer therapy. NOB induces apoptosis and cell cycle arrest in cancer cells. It can suppress migration and invasion of cancer cells via the inhibition of epithelial-to-mesenchymal transition (EMT) and EMT-related factors such as TGF-β, ZEB, Slug, and Snail. Besides, NOB inhibits oncogene factors such as STAT3, NF-κB, Akt, PI3K, Wnt, and so on. Noteworthy, onco-suppressor factors such as microRNA-7 and -200b undergo upregulation by NOB in cancer therapy. These onco-suppressor and oncogene pathways and mechanisms are discussed in this review.
Insights
Nobiletin (NOB), a natural flavone from citrus fruits, shows significant antitumor potential by inducing cancer cell apoptosis and halting cell cycle progression. It also inhibits cancer cell migration and invasion, offering a promising avenue for novel cancer therapies.
Area of Science:
- Pharmacology
- Oncology
- Natural Products Chemistry
Background:
- Cancer therapy research actively seeks novel antitumor drugs due to acquired drug resistance.
- Natural compounds offer multi-targeting capabilities, making them promising candidates for cancer treatment.
- Nobiletin (NOB), a flavone from citrus fruits, exhibits diverse pharmacological activities, including antitumor effects.
Purpose of the Study:
- To comprehensively review the efficacy of Nobiletin (NOB) in cancer therapy.
- To elucidate the mechanisms by which NOB exerts its antitumor effects.
- To discuss the role of NOB in modulating oncogenic and tumor-suppressive pathways.
Main Methods:
- Literature review of studies investigating Nobiletin's antitumor activity.
- Analysis of NOB's effects on cancer cell apoptosis and cell cycle.
- Examination of NOB's impact on cancer cell migration, invasion, and epithelial-to-mesenchymal transition (EMT).
- Investigation of NOB's modulation of key oncogenic (STAT3, NF-κB, Akt, PI3K, Wnt) and tumor-suppressive (microRNA-7, -200b) pathways.
Main Results:
- Nobiletin (NOB) effectively induces apoptosis and cell cycle arrest in cancer cells.
- NOB suppresses cancer cell migration and invasion by inhibiting epithelial-to-mesenchymal transition (EMT) and related factors (TGF-β, ZEB, Slug, Snail).
- NOB downregulates crucial oncogenic factors including STAT3, NF-κB, Akt, PI3K, and Wnt.
- NOB upregulates tumor-suppressive factors such as microRNA-7 and microRNA-200b.
Conclusions:
- Nobiletin (NOB) demonstrates significant potential as an anticancer agent through multiple mechanisms.
- NOB's ability to induce apoptosis, inhibit metastasis, and modulate key signaling pathways supports its therapeutic value.
- Further research into Nobiletin could lead to the development of novel, natural-based cancer therapies.
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