Methyl alcohol extract of marine green alga (Linnaeus) J. Agardh. induces reactive oxygen species-dependent growth arrest and apoptosis in human hepatocellular carcinoma Hep3B cells.

BACKGROUND/OBJECTIVES: Although seaweed has recently been attracting attention as an important source for the control of numerous diseases including cancer, studies on the anti-cancer activity of the green alga (Linnaeus) J. Agardh. are still insufficient. The purpose of this study was to investigate the anti-cancer activity of the green alga in human hepatocellular carcinoma Hep3B cells.

MATERIALS/METHODS: The effect of methyl alcohol extract of (MEEL) on cell viability and the induction of cell cycle arrest and apoptosis of Hep3B cells was investigated. To evaluate the anti-cancer activity mechanism of MEEL, the production of reactive oxygen species (ROS) and mitochondrial membrane potential were detected. We also investigated changes in the expression of key regulators of cell cycle and apoptosis.

RESULTS

Our results indicated that MEEL-induced inhibition of Hep3B cell proliferation was associated with G1 phase cell cycle arrest, along with the induction of cyclin-dependent kinase (Cdk) inhibitor p21 expression, suppression of cyclin D1 and E expression, and dephosphorylation of retinoblastoma protein (pRB). In addition, MEEL markedly enhanced the complex formation between p21 and Cdk4/6, as well as pRB and the transcription factor E2Fs, respectively. MEEL also induced apoptosis by activation of caspases. Moreover, MEEL interfered with mitochondrial integration by altering the level of Bcl-2 family proteins to increase cytoplasmic release of cytochrome . Furthermore, MEEL significantly enhanced the generation of ROS, whereas ROS scavenger restored reduced viability by attenuating MEEL-mediated growth arrest and apoptosis.

CONCLUSION

Collectively, the present findings demonstrate that the antiproliferative efficacy of MEEL in Hep3B cells can be achieved through ROS-dependent pathway.