ABSTRACT
Colorectal cancer (CRC) is one of the most prevalent and lethal cancer types around the world. Most of the CRC patients are treated with chemotherapeutic drugs alone or combined. However, up to 90% of metastatic cancer patients experience the failure of treatment mostly because of the acquired drug resistance, which can be led to multidrug resistance (MDR). In this study, we reviewed the recent literature which studied potential CRC MDR reversal agents among herbal medicines (HMs). Among abundant HMs, 6 single herbs, Andrographis paniculata, Salvia miltiorrhiza, Hedyotis diffusa, Sophora flavescens, Curcuma longa, Bufo gargarizans, and 2 formulae, Pien Tze Huang and Zhi Zhen Fang, were found to overcome CRC MDR by two or more different mechanisms, which could be a promising candidate in the development of new drugs for adjuvant CRC chemotherapy.
ABSTRACT
Baicalein, a natural flavonoid obtained from the rhizome of Scutellaria baicalensis Georgi, has been reported to have anticancer activities in several human cancer cell lines. However, its antimetastatic effects and associated mechanisms in melanoma cells have not been extensively studied. The current study examined the effects of baicalein on cell motility and anti-invasive activity using mouse melanoma B16F10 cells. Within the noncytotoxic concentration range, baicalein significantly inhibited the cell motility and invasiveness of B16F10 cells in a concentration-dependent manner. Baicalein also reduced the activity and expression of matrix metalloproteinase (MMP)-2 and -9; however, the levels of tissue inhibitor of metalloproteinase-1 and -2 were concomitantly increased. The inhibitory effects of baicalein on cell motility and invasiveness were found to be associated with its tightening of tight junction (TJ), which was demonstrated by an increase in transepithelial electrical resistance and downregulation of the claudin family of proteins. Additionally, treatment with baicalein markedly reduced the expression levels of lipopolysaccharide-induced phosphorylated Akt and the invasive activity in B16F10 cells. Taken together, these results suggest that baicalein inhibits B16F10 melanoma cell migration and invasion by reducing the expression of MMPs and tightening TJ through the suppression of claudin expression, possibly in association with a suppression of the phosphoinositide 3-kinase/Akt signaling pathway.