Methanol Extract of Aerial Parts of Pavetta indica L. Enhances the Cytotoxic Effect of Doxorubicin and Induces Radiation Sensitization in MDA-MB-231 Triple-Negative Breast Cancer Cells

摘要

Pavetta indica L. is used in traditional medicine for the treatment of various diseasesincluding hemorrhoids, headache, urinary conditions, ulcerated nose, and dropsy. However, nostudy has evaluated the anticancer effect of P. indica L. In this study, we found that a methanolextract of the leaves and branches of P. indica L. (MEPI) caused cell‐cycle arrest at the sub‐G1 phaseand induced apoptosis, as indicated by the activation of caspase‐8, ‐3, ‐7, and c‐PARP. Westernblotting revealed that MEPI significantly reduced the levels of markers of theepithelial‐mesenchymal transition, such as Vimentin, Snail, Slug, and matrix metallopeptidase 9.Notably, the expression of multidrug resistance‐associated protein 1 in triple negative breast cancer(TNBC) was significantly decreased by MEPI. Moreover, the co‐treatment with MEPI anddoxorubicin resulted in a synergistic reduction in cell viability. MEPI also induced radiationsensitization of TNBC cells. Gas chromatography‐mass spectrometry analysis revealed that5,6‐dehydrokawain (DK) is the major constituent of MEPI. Interestingly, DK exerted significantanti‐invasive and anti‐metastatic effects. Our results provide a strong rationale for investigating themolecular mechanisms of action of MEPI in TNBC.