Appl Microbiol Biotechnol. 2009 Jun 20; Kong WJ, Wang JB, Jin C, Zhao YL, Dai CM, Xiao XH, Li ZLUsing the 3114/3115 thermal activity monitor (TAM) air isothermal microcalorimeter, ampoule mode, the heat output of Candida albicans growth at 37 degrees C was measured, and the effect of emodin on C. albicans growth was evaluated by microcalorimetry coupled with chemometric methods. The similarities between the heat flow power (HFP)-time curves of C. albicans growth affected by different concentrations of emodin were calculated by similarity analysis (SA). In the correspondence analysis (CA) diagram of eight quantitative parameters taken from the HFP-time curves, it could be deduced that emodin had definite dose-effect relationship as the distance between different concentrations of it increased along with the dosage and the effect. From the principal component analysis (PCA) on eight quantitative parameters, the action of emodin on C. albicans growth could be easily evaluated by analyzing the change of values of the main two parameters, growth rate constant k (2) and maximum power output [Formula: see text]. The coherent results of SA, CA, and PCA showed that emodin at different concentrations had different effects on C. albicans growth metabolism: A low concentration (0-10 mug ml(-1)) poorly inhibited the growth of C. albicans, and a high concentration (15-35 mug ml(-1)) could notably inhibit growth of this fungus. This work provided a useful idea of the combination of microcalorimetry and chemometric analysis for investigating the effect of drug and other compounds on microbes.

J Cell Mol Med. 2009 Jun 16; Dai M, Miao ZH, Ren X, Tong LJ, Yang N, Li T, Lin LP, Shen YM, Ding JAbstract The macrolide compound MFTZ-1 has been identified as a novel topoisomerase II (Top2) inhibitor with potent in vitro and in vivo anti-tumor activities. In this study, we further examined the effects of MFTZ-1 on hypoxia-inducible factor-1alpha (HIF-1alpha) accumulation, vascular endothelial growth factor (VEGF) secretion and angiogenesis. MFTZ-1 reduced HIF-1alpha accumulation driven by hypoxia or growth factors in human cancer cells. Mechanistic studies revealed that MFTZ-1 did not affect the degradation of HIF-1alpha protein or the level of HIF-1alpha mRNA. By contrast, MFTZ-1 apparently inhibited constitutive and inducible activation of both phosphatidylinositol-3-kinase (PI3K)-Akt and p42/p44 mitogen-activated protein kinase (MAPK) pathways. Further studies revealed that MFTZ-1 abrogated the HIF-1alpha-driven increase in VEGF mRNA and protein secretion. MFTZ-1 also lowered the basal level of VEGF secretion. The results reveal an important feature that MFTZ-1 can reduce constitutive, HIF-1alpha-independent VEGF secretion and concurrently antagonize inducible, HIF-1alpha-dependent VEGF secretion. Moreover, MFTZ-1 disrupted tube formation of human umbilical vein endothelial cells (HUVECs) stimulated by hypoxia with low-concentration serum or by serum at normoxia, and inhibited HUVECs migration at normoxia. MFTZ-1 also prevented microvessel outgrowth from rat aortic ring. These data reflect the potent anti-angiogenesis of MFTZ-1 under different conditions. Furthermore, using specific small interfering RNA targeting Top2alpha or Top2-defective HL60/MX2 cells, we showed that MFTZ-1 affected HIF-1alpha accumulation and HUVECs tube formation irrelevant to its Top2 inhibition. Taken together, our data collectively reveal that MFTZ-1 reduces constitutive and inducible HIF-1alpha accumulation and VEGF secretion possibly via PI3K-Akt and MAPK pathways, eliciting anti-angiogenesis independently of its Top2 inhibition.