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

L. is used in traditional medicine for the treatment of various diseases including hemorrhoids, headache, urinary conditions, ulcerated nose, and dropsy. However, no study has evaluated the anticancer effect of L. In this study, we found that a methanol extract of the leaves and branches of L. (MEPI) caused cellcycle arrest at the sub-G1 phase and induced apoptosis, as indicated by the activation of caspase-8, -3, -7, and c-PARP. Western blotting revealed that MEPI significantly reduced the levels of markers of the epithelial-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 and doxorubicin resulted in a synergistic reduction in cell viability. MEPI also induced radiation sensitization of TNBC cells. Gas chromatography-mass spectrometry analysis revealed that 5,6-dehydrokawain (DK) is the major constituent of MEPI. Interestingly, DK exerted significant anti-invasive and anti-metastatic effects. Our results provide a strong rationale for investigating the molecular mechanisms of action of MEPI in TNBC.