Diferuloylmethane augments the cytotoxic effects of piplartine isolated from Piper chaba.
Toxicol In Vitro. 2009 Jun 3;
Authors: Jyothi D, Vanathi P, Gowri PM, Rao VR, Rao JM, Sreedhar AS
Natural compound based anticancer drug discovery is gaining interest against a wide variety of tumors. E-piplartine (trans-piplartine), a natural compound isolated from Piper chaba roots is examined against rat histiocytoma (BC-8), mouse embryonal carcinoma (PCC4), mouse macrophages (P388D1 and J774), and human neuroblastoma (IMR-32) tumor cells. While Z-piplartine (cis-piplartine) failed to induce cytotoxicity (even at higher concentrations, 50 M), E-piplartine induced a dose-dependent cytotoxicity (2 muM- 24 muM) in different tumor cells. The combinatorial treatment of piplartine with diferuloylmethane (curcumin), an anti-inflammatory and anti-cancer agent, significantly enhanced the piplartine induced cytotoxicity in tumor cells. Diferuloylmethane itself is not cytotoxic at 15 muM concentration; however, potentiated the piplartine induced cytotoxicity. The tumor cell killing with piplartine is preceded by G1 cell cycle arrest, and surpassed diferuloylmethane induced G2/M arrest when used in combination. In PCC4 cells, piplartine inhibited the cell cycle progression by inactivating cdk2 and destabilizing cyclin D1, whereas diferuloylmethane combination inhibited the ERK1/2 and Raf-1 signaling in addition to the inhibition of cell cycle progression. The over expression of heat shock protein 70, Hsp70 in rat histiocytic tumor cells interfered with piplartine induced cytotoxicity, hence, a cross talk between stress response and anticancer agents is presented. Our data demonstrates the biological and medicinal importance of piplartine isolated from the roots of Piper chaba, and indicates that E-piplartine may be a promising candidate to use in combinatorial treatments to combat cancer.
PMID: 19501152 [PubMed - as supplied by publisher]