Multidrug resistance (MDR) is one of the main obstacles in tumor chemotherapy. A promising approach to solving this problem is to utilize a nontoxic and potent modulator able to reverse MDR, which in combination with anticancer drugs increases the anticancer effect. Experiments were carried out to examine the potential of tetrandrine (Tet) as a MDR-reversing agent. Survival of cells incubated with Tet at 2.5 micromol/l for 72 h was over 90%. Tet at 2.5 micromol/l almost completely reversed resistance to vincristine (VCR) in KBv200 cells. Tet at a concentration as low as 0.625 micromol/l produced a 7.6-fold reversal of MDR, but showed no effect on the sensitivity of drug-sensitive KB cells in vitro. In the KBv200 cell xenograft model in nude mice, neither Tet nor VCR inhibited tumor growth. However, VCR and Tet combined inhibited tumor growth by 45.7%, 61.2% and 55.7% in three independent experimental settings. In the KB cell xenograft model in nude mice, Tet did not inhibit tumor growth, but VCR and the combination of VCR and Tet inhibited tumor growth by 40.6% and 41.6%, respectively. Mechanism studies showed that Tet inhibited [(3)H]azidopine photoaffinity labeling of P-gp and increased accumulation of VCR in MDR KBv200 cells in a concentration-dependent manner. The results suggest that Tet is a potent MDR-reversing agent in vitro and in vivo. Its mechanism of action is via directly binding to P-gp and increasing intracellular VCR accumulation.

AMAD, an emodin azide methyl anthraquinone derivative, was extracted from the nature giant knotweed rhizome of traditional Chinese herbs. Here, we investigated the anticancer activities and signaling pathways implicated in AMAD-induced apoptosis in human breast cancer cell lines MDA-MB-453 and human lung adenocarcinoma Calu-3 cells. AMAD was found to have a potent cytotoxic effect on both cell lines. Hoechst 33258 staining and Annexin V/propidium iodide double staining exhibited the typical nuclear features of apoptosis and increased the proportion of apoptotic Annexin V -positive cells in a dose-dependent manner, respectively. Moreover, this apoptotic induction was associated with a collapse of the mitochondrial membrane potential and activated caspases (cysteine aspartase) cascade involving in caspase-8, caspase-9, caspase-3, and poly(ADP-ribose) polymerase cleavage in a concentration-dependent manner. It was noteworthy that AMAD also effectively cleaved Bid, a BH3 domaincontaining proapoptotic Bcl-2 family member, and induced the subsequent release of cytochrome c from mitochondria into the cytosol. Furthermore, suppression of caspase-8 activity with Z

Two new cytotoxic tetracyclic tetraterpenoids, methyl tortuoate A (1) and methyl tortuoate B (2), along with the known methyl sartortuoate (3) were isolated from the soft coral Sarcophyton tortuosum. The structures of 1 and 2 were established by spectroscopic methods, mainly on the basis of 2D NMR techniques, and were confirmed by single-crystal X-ray diffraction analysis. The cytotoxic activities of these compounds were carried out in vitro on human nasophyringeal carcinoma (CNE-2) and murine lymphocytic leukemia (P-388) tumor cell lines.

Five new cembrane diterpenoids, sarcrassins A-E (1-5) along with a known compound, emblide (6), have been isolated from the soft coral Sarcophyton crassocaule collected from the Bay of Sanya, Hainan Island, China. The structures of 1-5 were determined by spectroscopic methods including 1D and 2D NMR techniques. Their relative configurations were determined by NMR data and NOESY experiments. Compounds 2, 4, and 6 exhibited significant cytotoxic activities against KB cell lines with IC50 values of 5.0, 4.0, and 5.0 microg/mL, respectively, while compounds 1 and 5 showed moderate cytotoxicity toward KB cell lines with IC50 values of 19.0 and 13.0 microg/mL, respectively.