?Background: Cancer caused by high-risk Human Papillomavirus (HPV), is a global health concern. The viral oncoproteins E6 and E7 are primarily responsible for inducing carcinogenesis. Chemotherapy treatments can cause serious side effects, in addition to loss of efficacy due to chemoresistance, drive the search for new therapies. Taraxacum officinale (dandelion) has traditional use against warts (HPV-associated) and reported antitumor activity, but no prior studies existed on its effect on HPV oncogenes.
Objectives: To evaluate the effects of the ethanolic root extract (R-EtOH) of T. officinale on viability, proliferation, migration, and cell death in cancer cell lines, and to investigate its impact on the expression of the HPV 16 and 18 E6/E7 oncogenes
Methods: Three cervical cancer (CC), cell lines were used: CaSki (HPV16+), HeLa (HPV18+), and C33A (HPV negative), along with the non-cancerous HaCaT line. R-EtOH cytotoxicity was determined via the MTT assay. Effects on survival, migration, apoptosis (TUNEL/Annexin V), autophagy (LC3 detection), and E6/E7 mRNA expression (qPCR) were evaluated using the IC20 and IC50 concentrations of the extract. Phytochemical composition was analyzed by HPLC-DAD-ESI-QTOF.
Results: The R-EtOH extract significantly reduced the expression of HPV 16 and 18 E6 and E7 oncogenes in CaSki and HeLa cells in a dose-dependent manner. This is the first report demonstrating that a dandelion extract directly inhibits the production of these key oncoproteins in cervical cancer. The extract exhibited potent selective cytotoxicity towards CC cells, with minimal effect on non-tumor HaCaT cells. Innovatively, it induced cell death through two programmed pathways: apoptosis and autophagy, a dual mechanism that could overcome therapeutic resistance. R-EtOH strongly inhibited clonogenic proliferation and cell migration. Phytochemical analysis revealed a complex mixture including phenolic acids and sesquiterpene lactones, which may suggest a synergistic effect.
Conclusions: R-EtOH from T. officinale is a promising extract against HPV-associated cervical cancer. Its mechanism of action, based on the inhibition of HPV E6/E7 oncoprotein expression and the simultaneous induction of apoptosis and autophagy, along with its selectivity, positions it as a candidate for the study of future therapies. These findings justify further studies to isolate the active ingredients and evaluate their efficacy, thus opening a new avenue for the prevention and treatment of cancer associated with HPV.