Withanolides are steroidal lactones that were originally isolated from Withania somnifera, one of the most important herbs used as a traditional remedy for several illnesses in Asian countries (1). These compounds are biologically active and have been shown to inhibit the enzymatic activity of cyclooxygenase-2 and suppress inflammation (2). In addition, recent studies demonstrate that withanolides exhibit anti-cancer effect on human lung, colon, and breast cancer cells in vitro and exert immunopotentiating activity in vivo (3, 4). Several potential mechanisms have been implicated in the inhibition of tumorigenesis by withanolides. First, withanolides induce growth arrest and apoptosis in cancer cells (4, 5). Second, withanolides can inhibit angiogenesis by suppressing endothelial cell proliferation (6). Third, withanolides can reduce cancer cell invasion and metastasis (7). These data suggest that withanolides may be developed as a novel class of anti-cancer drugs.Lymph node invasion by cancer cells is an important step for tumor metastasis and is frequently correlated with early recurrence and poor prognosis. However, the underlying mechanism by which cancer cells metastasize into peripheral lymphatic capillaries is poorly defined. Recent studies indicate that the interaction between chemokine CCL21 and its cognate receptor CCR7 may play an important role in this process (8, 9). The hypothesis suggests that lymphatic endothelial cells (LECs) 2 express and release chemotactic factors such as CCL19 and CCL21 to direct cancer cells with high expression of chemokine receptor CCR7 to grow and migrate toward lymphatic capillaries (10 -12). Indeed, many highly metastatic cancer cells express large amount of CCR7 receptor (13,14), and CCR7 expression is associated with lymph node metastasis in breast, lung, gastric, esophageal cancer, and melanoma (15-19). It is possible that inhibition of CCR7 expression or block of CCL21-CCR7 interaction may cause reduction of lymph node invasion and tumor metastasis. However, the control of CCR7 gene transcription in cancer cells is largely unclear, and no natural products have been shown to regulate CCR7 expression.We have isolated a new bioactive withanolide tubocapsanolide A (Tubo A) from Tubocapsicum anomalum (20). Tubo A exhibited cytotoxic activity on various types of human cancer cells (20). In addition, our recent results demonstrated that Tubo A suppressed the transcription of Skp2 oncogene and up-regulated cyclin-dependent kinase inhibitory proteins p27