piperidines and artemisinin

Our previous study found that the combination of halofuginone (HF) and artemisinin (ATS) synergistically arrest colorectal cancer (CRC) cells at the G1/G0 phase of the cell cycle; however, it remains unclear whether HF-ATS induces cell death. Here we report that HF-ATS synergistically induced caspase-dependent apoptosis in CRC cells. Specifically, both

Topics: Antineoplastic Agents; Apoptosis; Artemisinins; Autophagy; Caspase 8; Caspase 9; Cell Line, Tumor; Colorectal Neoplasms; Drug Synergism; Enzyme Activation; Humans; Piperidines; Quinazolinones; Receptor Cross-Talk

Combinational drug therapy is one of the most promising strategies in modern anticancer research. Traditional Chinese medicine (TCM) formulas represent a wealth of complex combinations proven successful over centuries of clinical application. One such formula used to treat a variety of diseases, including cancer, contains two herbs, whose main active components are Halofuginone (HF) and Artemisinin (ATS). Here we studied the anticancer synergism of HF and ATS in various cancer cell lines and in a xenograft nude mice model. We found that the HF-ATS combination arrested more cells at the G1/G0 phase than either one alone, with the concomitant increased levels of CDK2 inhibitors, p21Cip1 and p27Kip1. By knocking down p21Cip1 and p27Kip1 separately or simultaneously in HCT116 cells and MCF-7 cells, we found that p21Cip1 was required for HF induced G1/G0 arrest, whereas p21Cip1 and p27Kip1 were both required for ATS or HF-ATS combination-mediated cell cycle arrest. Moreover, HF-ATS combination synergistically inhibited tumor growth in xenograft nude mice, and this was associated with the increased levels of p21Cip1 and p27Kip1. Collectively, these data indicate that the upregulation of p21Cip1 and p27Kip1 contributes to the synergistic anticancer effect of the HF-ATS combination.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Artemisinins; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Drug Synergism; Female; G1 Phase; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Piperidines; Quinazolinones; Resting Phase, Cell Cycle; Up-Regulation

Recent studies have proposed curcumin as a potential partner for artemisinin in artemisinin combination therapies to treat malaria infections. The efficacy of curcumin alone and in combination with artemisinin was evaluated on a clone of Plasmodium chabaudi selected for artemisinin resistance in vivo. The addition of piperine as an enhancer of curcumin activity was also tested. Results indicated that curcumin, both alone and in combination with piperine had only a modest antimalarial effect and was not able to reverse the artemisinin-resistant phenotype or significantly affect growth of the tested clone when used in combination with artemisinin. This is in contrast with previous in vivo work and calls for further experimental evaluation of the antimalarial potential of curcumin.

Topics: Administration, Oral; Alkaloids; Animals; Anti-Infective Agents; Artemisinins; Benzodioxoles; Biological Availability; Curcumin; Drug Resistance; Drug Therapy, Combination; Malaria; Male; Mice; Parasitemia; Piperidines; Plasmodium chabaudi; Polyunsaturated Alkamides