Bioactive plant and fungal metabolites in oral cancer: molecular mechanisms and translational potential
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Published on: March 31, 2021
Yi Luo1,2, Xijie Wu1,2, Wenjing Chen1,2
1Department of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
Abstract:
Oral cancer remains a major global health burden. Current therapies are often limited by recurrence, drug resistance, and systemic toxicity. Natural bioactive metabolites, particularly those derived from medicinal plants used in Traditional Chinese Medicine are increasingly investigated as multitarget anticancer leads. In this review, we integrated evidence from studies published between January 2010 and June 2025. We summarize representative flavonoids, terpenoids, phenolic metabolites, alkaloids, polysaccharides, and quinones evaluated in oral cancer models. Reported activities include suppression of proliferation, induction of apoptosis and autophagy, inhibition of epithelial-mesenchymal transition and angiogenesis, and modulation of tumor metabolism and immune pathways. However, the current evidence base remains largely preclinical and frequently relies on simplified in vitro assays. Pharmacokinetic bridging, toxicity evaluation, and clinically relevant validation are still limited. Importantly, several polyphenolic metabolites exhibit pan-assay interference (PAINS) liabilities, requiring cautious interpretation of pathway-level findings. Advances in nano-delivery systems, rational structural optimization, and combination strategies may improve exposure and selectivity. Future work should emphasize PAINS-aware pharmacological rigor, orthogonal target validation, advanced translational models, and biomarker-driven clinical trials to support the development of genuinely druggable natural metabolite candidates for oral cancer management.
Insights
Natural compounds from Traditional Chinese Medicine show promise for oral cancer treatment by targeting multiple pathways. However, more rigorous preclinical and clinical studies are needed to overcome limitations and ensure safety.
Area of Science:
- Natural Products Chemistry
- Oncology
- Pharmacology
Background:
- Oral cancer presents significant therapeutic challenges due to recurrence, drug resistance, and toxicity of current treatments.
- Medicinal plants from Traditional Chinese Medicine offer a rich source of bioactive metabolites with potential anticancer properties.
- Natural compounds are being explored as multitarget agents to overcome limitations in oral cancer therapy.
Purpose of the Study:
- To review and summarize the evidence on natural bioactive metabolites from medicinal plants evaluated in oral cancer models.
- To highlight the diverse anticancer activities of these metabolites, including effects on proliferation, apoptosis, and angiogenesis.
- To identify current limitations and future directions for developing natural metabolite-based oral cancer therapies.
Main Methods:
- Systematic literature review of studies published between January 2010 and June 2025.
- Analysis of preclinical data on flavonoids, terpenoids, alkaloids, and other metabolites in oral cancer models.
- Evaluation of reported mechanisms of action, including effects on cell signaling, metabolism, and immunity.
Main Results:
- Various natural metabolites, including flavonoids and terpenoids, demonstrated significant anticancer activities in preclinical oral cancer models.
- Reported activities encompass suppression of proliferation, induction of apoptosis and autophagy, and inhibition of angiogenesis and epithelial-mesenchymal transition.
- The current evidence base is predominantly preclinical, with limited pharmacokinetic and toxicity data, and concerns regarding pan-assay interference (PAINS) liabilities.
Conclusions:
- Natural bioactive metabolites hold promise as novel therapeutic leads for oral cancer management.
- Further research focusing on PAINS-aware validation, pharmacokinetic studies, and advanced translational models is crucial.
- Development of nano-delivery systems, structural optimization, and combination strategies may enhance the clinical utility of these compounds.
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