The present study investigated rhenium (I) tricarbonyl-complex (RTCC) as anticancer agent against OE-33 and EC9706 esophageal carcinoma cells and explored the underlying mechanism. Treatment with RTCC led to a dose-dependent reduction in viability of OE-33 and EC9706 cells in 0.37 to 96 mu M concentration range. The viability of OE-33 and EC9706 cells was reduced to 22 and 18%, respectively, on treatment with 96 pM RTCC. Colony formation was significantly (p < 0.05) reduced in OE-33 and EC9706 cells on treatment with 12 mu M RTCC. Treatment with RTCC at 12 mu M led to a significant (p < 0.05) increase in apoptotic cell fraction in OE-33 and EC9706 cell cultures. The expression of Bcl-2 protein was suppressed and that of Bax promoted in OE-33 and EC9706 cells by RTCC treatment. The average number of OE-33 and EC9706 cells undergoing invasion and migration showed a significant (p < 0.05) decrease on treatment with 12 mu M RTCC. Treatment with RTCC led to a prominent suppression in expression of MMP2 and MMP-9 in OE-33 and EC9706 cells. Moreover, the expression of E-cadherin was found to be markedly higher in OE-33 and EC9706 cells on treatment with RTCC. In summary, RTCC treatment inhibits esophageal carcinoma cell proliferation, suppresses colony formation ability and activates apoptotic pathway. Thus, RTCC acts as effective anti-proliferative agent for esophageal carcinoma cells and needs to be investigated further as chemotherapeutic molecule.