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Natural bioactive compounds and FOXO3a in cancer therapeutics: An update
Suryaa Manoharan1, Kunjkumar Prajapati1, Ekambaram Perumal1
1Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, India.
Abstract:
Forkhead box protein 3a (FOXO3a) is a transcription factor that regulates various downstream targets upon its activation, leading to the upregulation of tumor suppressor and apoptotic pathways. Hence, targeting FOXO3a is an emerging strategy for cancer prevention and treatment. Recently, Natural Bioactive Compounds (NBCs) have been used in drug discovery for treating various disorders including cancer. Notably, several NBCs have been shown as potent FOXO3a activators. NBCs upregulate FOXO3a expressions through PI3K/Akt, MEK/ERK, AMPK, and IκB signaling pathways. FOXO3a promotes its anticancer effects by upregulating the levels of its downstream targets, including Bim, FasL, and Bax, leading to apoptosis. This review focuses on the dysregulation of FOXO3a in carcinogenesis and explores the potent FOXO3a activating NBCs for cancer prevention and treatment. Additionally, the review evaluates the safety and efficacy of NBCs. Looking ahead, NBCs are anticipated to become a cost-effective, potent, and safer therapeutic option for cancer, making them a focal point of research in the field of cancer prevention and treatment.
Insights
Natural Bioactive Compounds (NBCs) activate the FOXO3a transcription factor, a key player in tumor suppression and apoptosis. This review explores NBCs as a promising, safe, and cost-effective strategy for cancer prevention and treatment.
Area of Science:
- Molecular Biology
- Biochemistry
- Oncology
Background:
- Forkhead box protein 3a (FOXO3a) is a critical transcription factor involved in regulating tumor suppressor and apoptotic pathways.
- Dysregulation of FOXO3a is implicated in various cancers, making it a target for therapeutic intervention.
- Natural Bioactive Compounds (NBCs) are increasingly recognized for their potential in drug discovery, including cancer treatment.
Purpose of the Study:
- To review the role of FOXO3a in carcinogenesis.
- To explore Natural Bioactive Compounds (NBCs) that activate FOXO3a for cancer prevention and treatment.
- To evaluate the safety and efficacy of NBCs as anticancer agents.
Main Methods:
- Literature review focusing on FOXO3a's role in cancer.
- Identification and analysis of NBCs that modulate FOXO3a expression and activity.
- Examination of signaling pathways (PI3K/Akt, MEK/ERK, AMPK, IκB) involved in NBC-mediated FOXO3a activation.
- Review of downstream targets of FOXO3a (Bim, FasL, Bax) and their role in apoptosis.
Main Results:
- NBCs activate FOXO3a through multiple signaling pathways, including PI3K/Akt, MEK/ERK, AMPK, and IκB.
- Activated FOXO3a upregulates pro-apoptotic genes such as Bim, FasL, and Bax, promoting cancer cell death.
- Several NBCs demonstrate potent FOXO3a-activating properties with potential anticancer effects.
Conclusions:
- FOXO3a is a crucial target for cancer therapy due to its role in apoptosis.
- NBCs represent a promising avenue for activating FOXO3a, offering a potentially cost-effective, potent, and safer therapeutic strategy for cancer.
- Further research into NBCs for cancer treatment is warranted, focusing on safety and efficacy.
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