Nanoliposomal Curcumin Suppresses AKT Phosphorylation and Induced Apoptosis in HeLa Cells: Implications for Overcoming Cisplatin Resistance in Cervical Cancer

Persistent HPV-18 infection often leads to the activation of the constitutive PI3K/AKT pathway in cervical cancer cells, establishing an anti-apoptotic environment that underlies both tumor progression and resistance to platinum-based chemotherapy. Nanoliposomal curcumin (Cur-NLPs) offers a targeted delivery strategy capable of modulating this pathway with enhanced intracellular bioavailability. Therefore, this study aims to characterize the capacity of Cur-NLPs as a cervical cancer model, administered as a single agent, to induce apoptosis and attenuate AKT phosphorylation in HeLa, as well as compare its AKT modulation profile with cisplatin. HeLa cells received Cur-NLPs at 3 concentrations (100, 150, and 200 µg/mL) or cisplatin (5 µg/mL) for 24 hours. Apoptotic cell populations were quantified using Annexin V/PI flow cytometry. AKT phosphorylation (pAKT Tyr315) was then evaluated by immunofluorescence and quantified using Corrected Total Cell Fluorescence (CTCF) through FIJI/ImageJ. Statistical analysis was carried out using the Kruskal-Wallis test with Bonferroni-corrected Dunn’s post-hoc test and Spearman’s rank correlation. The results showed that Cur-NLPs induced a dose-associated increase in apoptosis across all treatment concentrations. However, no statistically significant difference was observed between any Cur_NLPs group and untreated cells, with cisplatin producing significant apoptosis induction. The treatment also suppressed AKT phosphorylation in a dose-dependent manner, with significant reduction achieved at 200 µg/mL. Cisplatin maintained AKT phosphorylation at levels comparable to untreated cells, confirming its activation of AKT-mediated survival signaling as a resistance mechanism. These results provide a mechanistic rationale for Cur-NLPs as an adjuvant agent to counteract cisplatin-induced AKT-mediated resistance in cervical cancer.