Plant-Derived Bioactive Compounds, Cancer Stemness and Cellular Senescence: A Narrative Review of Preclinical Evidence and Translational Relevance to Cancer Recurrence and Drug Resistance
- 1School of Health Science, IMU University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia
- 2Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, A25-303 Room, Life Sciences Hall, No. 300, Syuefu Road, National Chiayi University, Chiayi City 600355, Taiwan
- 3School of Health Science, Division of Applied Biomedical Science and Biotechnology, IMU University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia
Abstract
Background/Objectives: Cancer recurrence and drug resistance arise from tumour-cell plasticity and microenvironmental adaptations that may persist after treatment. Cancer stem cells (CSCs) are associated with self-renewal, tumour initiation, residual disease, and treatment tolerance, whereas cellular senescence has context-dependent effects. Although therapy-induced senescence may restrict tumour-cell proliferation, persistent senescent tumour or stromal cells and their senescence-associated secretory phenotype (SASP) can, in selected models, promote inflammatory signalling, stemness-associated phenotypes and therapeutic resistance. This narrative review critically evaluates preclinical and translational evidence concerning curcumin, resveratrol, epigallocatechin gallate, berberine, piperine and shikonin as potential adjunctive modulators of CSCs and senescence-associated processes. Methods: Relevant literature was identified through searches of the MEDLINE/PubMed database from June 2000 and July 2026, using terms related to plant-derived bioactive compounds, CSCs, cellular senescence, SASP, recurrence and drug resistance. Evidence was evaluated according to model relevance, exposure, functional validation and whether it represented direct cross-axis evidence, intermediate mechanistic evidence, or marker- and pathway-level support. Results: Most studies examined CSCs and senescence as separate processes. Direct evidence showing that the same compound, within the same cancer model, modifies a validated cancer stem-cell function and a defined senescence or SASP and subsequently reduces resistance or recurrence is limited or absent. Moreover, poor bioavailability, variable formulations, potentially unachievable experimental exposures, drug interactions, tumour heterogeneity and limited clinical evidence constrain translation. Conclusions: Future studies should incorporate pharmacologically relevant exposures, functional and longitudinal endpoints, causal validation and biomarker-guided combination designs to determine whether these compounds can safely complement standard anticancer therapies.
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BibTeX
@article{naseer2026plantderived,
title = {{Plant-Derived Bioactive Compounds, Cancer Stemness and Cellular Senescence: A Narrative Review of Preclinical Evidence and Translational Relevance to Cancer Recurrence and Drug Resistance}},
author = {Sara Naseer and Wai-Yann Tan and Yin-Teng Sow and Zhi-Yin Wai and Sahana-Shri Ramanitharan and Paey-Ern Bay and Ching-Hsein Chen and Soi-Moi Chye},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18213522},
url = {https://www.mdpi.com/2072-6643/18/21/3522},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Plant-Derived Bioactive Compounds, Cancer Stemness and Cellular Senescence: A Narrative Review of Preclinical Evidence and Translational Relevance to Cancer Recurrence and Drug Resistance
AU - Sara Naseer
AU - Wai-Yann Tan
AU - Yin-Teng Sow
AU - Zhi-Yin Wai
AU - Sahana-Shri Ramanitharan
AU - Paey-Ern Bay
AU - Ching-Hsein Chen
AU - Soi-Moi Chye
PY - 2026
DA - 2026/10/26
JO - Nutrients
DO - 10.3390/nu18213522
UR - https://www.mdpi.com/2072-6643/18/21/3522
AB - Background/Objectives: Cancer recurrence and drug resistance arise from tumour-cell plasticity and microenvironmental adaptations that may persist after treatment. Cancer stem cells (CSCs) are associated with self-renewal, tumour initiation, residual disease, and treatment tolerance, whereas cellular senescence has context-dependent effects. Although therapy-induced senescence may restrict tumour-cell proliferation, persistent senescent tumour or stromal cells and their senescence-associated secretory phenotype (SASP) can, in selected models, promote inflammatory signalling, stemness-associated phenotypes and therapeutic resistance. This narrative review critically evaluates preclinical and translational evidence concerning curcumin, resveratrol, epigallocatechin gallate, berberine, piperine and shikonin as potential adjunctive modulators of CSCs and senescence-associated processes. Methods: Relevant literature was identified through searches of the MEDLINE/PubMed database from June 2000 and July 2026, using terms related to plant-derived bioactive compounds, CSCs, cellular senescence, SASP, recurrence and drug resistance. Evidence was evaluated according to model relevance, exposure, functional validation and whether it represented direct cross-axis evidence, intermediate mechanistic evidence, or marker- and pathway-level support. Results: Most studies examined CSCs and senescence as separate processes. Direct evidence showing that the same compound, within the same cancer model, modifies a validated cancer stem-cell function and a defined senescence or SASP and subsequently reduces resistance or recurrence is limited or absent. Moreover, poor bioavailability, variable formulations, potentially unachievable experimental exposures, drug interactions, tumour heterogeneity and limited clinical evidence constrain translation. Conclusions: Future studies should incorporate pharmacologically relevant exposures, functional and longitudinal endpoints, causal validation and biomarker-guided combination designs to determine whether these compounds can safely complement standard anticancer therapies.
SN - 2072-6643
ER -