Natural Triterpenoids in Cervical Cancer Models: A Review of Anticancer Effects and Immunomodulatory Potential

Cervical cancer (CC) remains a prominent global malignancy that severely threatens women’s health. Despite the limitations of conventional therapies, Traditional Chinese Medicine (TCM) offers distinct therapeutic advantages via multi-targeted bioactive constituents. Although immune checkpoint inhibitors and antibody-drug conjugates have redefined advanced CC management, recurrence and drug resistance underscore the critical need for novel adjuvant strategies. Natural triterpenoids derived from TCM, including cucurbitacin, oleanolic acid, glycyrrhizin, ursolic acid, and betulinic acid, exhibit profound biological activities. In this review, we systematically synthesize preclinical evidence to demonstrate the efficacy of these triterpenoids against human HPV-associated CC models, including the HeLa, SiHa, CaSki, and TC-1 cell lines. Specifically, we categorize their mechanisms into two distinct tiers: (1) direct tumor-intrinsic cytotoxicity and molecular modulation, encompassing cell-cycle arrest, mitochondrial apoptosis, Atg5-dependent autophagy, ACSL4/GPX4-regulated ferroptosis, and proteasome-mediated HIF-1α degradation in CC cells; and (2) immunomodulatory properties, differentiating empirically observed immune effects in broader TCM or non-human-CC models (such as tumor PD-L1 suppression and systemic lymphocyte subset regulation) from putative microenvironmental consequences in CC (such as ferroptosis-derived DAMP-mediated dendritic cell priming, M2-to-M1 macrophage phenotypic shift, Th1/Th2 cytokine balance modulation, and the restoration of NK-cell immunosurveillance via HIF-1α degradation). Furthermore, we address critical translational bottlenecks, notably the heavy reliance on T-cell-deficient athymic nude mouse models, low oral bioavailability, and scarce clinical trial data. Ultimately, this review establishes a rigorous conceptual framework that decouples cell-intrinsic cytotoxicity from microenvironmental immune modulation, thereby guiding future bench-to-bedside translation.