Differential Cytotoxic and Selective Anticancer Profiles of Plant Extracts (Leaf, Bark, and Root): A Time-Dependent Evaluation of Solvent (aqueous, DCM, and Methanol) and Tissue Variability in HeLa Cervical Cells

Abstract

Cervical cancer is the fourth most common cancer among women globally. Resistance frequently restricts or prevents access to current medicines. Natural products present a possible substitute for anticancer drug discovery, especially those derived from understudied plants like Searsia rhemanniana. This study investigated the cytotoxic and selective anticancer properties of plant extracts prepared with three different solvents—aqueous, dichloromethane (DCM), and methanol (MeOH)—against HeLa cervical cancer cells over 24, 48, and 72 hours. Extracts derived from leaf, bark, and root tissues were compared to evaluate how solvent polarity and plant part influence biological activity. Across all exposure periods, DCM extracts consistently produced the most potent and dose-dependent suppression of cell viability, characterized by significantly lower IC₅₀ values and high curve-fitting reliability (R² = 0.95–0.99) compared to aqueous and methanolic extracts. Notably, the DCM bark and root fractions showed the strongest activity, with IC₅₀ values ranging between 22.7 and 43.4 µg/mL, while the leaf DCM extract displayed moderate effects. Two-way ANOVA revealed that both solvent type and plant tissue had a significant impact on cytotoxic outcomes (p < 0.001). The selective index (SI), determined using IC₅₀ values from normal Vero cells, showed that the DCM bark extract possessed the highest selectivity (SI > 1), indicating preferential toxicity toward cancer cells while sparing non-cancerous cells. The overall potency trend (DCM > MeOH > Aqueous) underscores the importance of solvent polarity in isolating lipophilic bioactive compounds such as terpenoids and alkaloid derivatives. Collectively, these results identify the DCM bark and root extracts as promising candidates for the development of selective, plant-derived anticancer agents, warranting further phytochemical and mechanistic investigations.