*6.2. Anti-Cancer Activity*

*T. impetiginosa* exhibits inhibitory effects on the growth of several human tumor cell lines, such as breast carcinoma (MCF-7), lung carcinoma (NCI-H460), cervical carcinoma (HeLa), and hepatocellular carcinoma (HepG2), and the GI50 values (corresponding to a sample concentration achieving 50% growth inhibition in human tumor cell lines) were 1.21, 1.03, 0.91, and 1.10 μg/mL, respectively [4]. Woo et al. [42] reported that β-lapachone isolated from *T. avellanedae* significantly inhibited the proliferation of human hepatoma cell line HepG2 by inducing apoptosis, which is associated with upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-2 and Bcl-XL expression, proteolytic activation of caspase-3 and -9, as well as degradation of poly (ADP-ribose) polymerase protein.

In a human breast carcinoma derived estrogen receptor (ER+) MCF-7 cells model, Taheebo showed antiproliferative effects by upregulating xenobiotic metabolism-specific genes (dual specific phosphatase genes) and apoptosis-specific genes and by downregulating estrogen response and cell cycle regulatory genes [24]. Particularly, Taheebo treatment upregulated the dual specific phosphatase (DUSP) gene family and downregulated cyclin A and cdk2, indicating that Taheebo also inhibited the MAPK signaling pathway and phosphorylation of the ER *N*-terminal AF-1 domain [24]. Junior et al. [62] found that the anti-cancer activity of *T. impetiginosa* was correlated with the presence of lapachol and β-lapachone in its constitution. It is noteworthy that *T. impetiginosa* not only displayed growth inhibition against various tumor cell lines in vitro but also prolonged the duration of survival in a number of mouse models in vivo. For example, Queiroz et al. [63] examined the effects of *T. avellanedae* (30–500 mg/kg) and the naphtoquinone β-lapachone (1–5 mg/kg) in Ehrlich's ascites tumor-bearing mice. They observed that *T. avellanedae* administration prolonged the lifespan of tumor-bearing mice by increasing the number of bone marrow granulocyte-macrophage colony-forming units and reducing colony-stimulating activity levels; the optimal biologically active dose was 120 mg/kg. In addition, Tahara et al. [14] found that naphthoquinones isolated from *T. avellanedae* markedly blocked the STAT3 pathway while reducing hyperactivation of these signals as well as inhibited growth of cancer cell lines.
