Plant-Derived Bioactive Compounds, Cancer Stemness and Cellular Senescence: A Narrative Review of Preclinical Evidence and Translational Relevance to Cancer Recurrence and Drug Resistance

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.