A study involving antioxidizability and cytotoxicity of two kinds of phenol from Ajania Salicifolia and their mechanisms of apoptosis / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To extract two kinds of phenols 4-hydroxy-3, 5-dimethoxy-4-(2-oxopropyl) cyclohexa-2, 5-dien-l-one and 6-methoxy-5,7-dihydroxy coumarin (named as I and H compounds respectively) from Ajania salicifolia and to investigate their antioxidation and cytotoxicity to tumors and explore their pro-apoptosis mechanism.</p><p><b>METHODS</b>The antioxidant activities of two compounds were assessed by ABTS and DPPH radical-scavenging assays. Two compounds were evaluated for their cytotoxicity against human chronic myelogenous leukemia (K562) cells using the MIT assay. The expression of NF-kappaB P65 mRNA in K562 apoptotic cells was measured by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR. In addition, protein expression levels of the NF-ICB P65, p-Akt, Fas, P-catenina and E-cadherin were also measured by Western blot.</p><p><b>RESULTS</b>(1) We found that compound I displayed significant inoxidizability, while compound II had no obvious antioxidizability. (2) In cytotoxicity experiments, compound I didn't display cytotoxicity while compound H displayed obvious cytotoxicity. (3) Compared with the blank group, the expression of NF-kappaB P65 mRNA in K562 cell after treatment with compound II was obviously up-regulated. (4) Compared with the blank group, the expression levels of NF-kappaB P65, Fas, beta-catenina and E-cadherin were significantly increased in compound II treated groups and it appeared obvious dose-effect relationship between the expression of protein and drug concentration.</p><p><b>CONCLUSION</b>Two phenols have obvious antioxidizability and cytotoxicity respectively. On the one hand, the tumor-suppressing mechanism of compound II maybe act by up-regulation the expression of NF-kappaB P65 and Fas protein; thereby, affecting the classical Fas apoptosis signaling pathways. On the other hand, it can also up-regulate the expression of protein beta-catenin and E-cadherin, which participate in the adhesion between cells, and accordingly, playing an important role in preventing the proliferation and metastasis of cancer cells.</p>

Inhibitory effects of Zengshengping fractions on DMBA-induced buccal pouch carcinogenesis in hamsters / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Zengshengping (ZSP) tablets had inhibitory effects on oral precancerous lesions by reducing the incidence of oral cancer. However, the severe liver toxicity caused by systemic administration of ZSP limits the long-term use of this anti-cancer drug. The purpose of this study was to evaluate the tumor inhibitory effects due to the topical application of extracts from ZSP, a Chinese herbal drug, on 7, 12-dimethlbenz(a)anthracene (DMBA) induced oral tumors in hamsters. The study also investigated the anti-cancer mechanisms of the ZSP extracts on oral carcinogenesis.</p><p><b>METHODS</b>DMBA (0.5%) was applied topically to the buccal pouches of Syrian golden hamsters (6 - 8 weeks old) three times per week for six weeks in order to induce the development of oral tumors. Different fractions of ZSP were either applied topically to the oral tumor lesions or fed orally at varying dosages to animals with oral tumors for 18 weeks. Tumor volume was measured by histopathological examination. Tumor cell proliferation was evaluated by counting BrdU labeled cells and by Western blotting for mitogen-activated protein kinase (MAPK) protein levels. The protein levels of apoptosis marker Caspase-3 and regulator Bcl-2 protein were also measured by Western blotting.</p><p><b>RESULTS</b>Topical application of DMBA to the left pouch of hamsters induced oral tumor formation. Animals treated with DMBA showed a loss in body weight while animals treated with ZSP maintained normal body weights. Both the ZSP n-butanol fraction and water fraction significantly reduced tumor volume by 32.6% (P < 0.01) and 22.9% (P < 0.01) respectively. Topical application of ZSP also markedly decreased the BrdU-positive cell numbers in oral tumor lesions and reduced the expression level of MAPK. In addition, ZSP promoted tumor cell apoptosis by increasing Caspase-3 expression but decreasing Bcl-2 protein production.</p><p><b>CONCLUSION</b>The n-butanol and water fractions of ZSP are effective at inhibiting tumor cell proliferation and stimulating apoptosis in oral cancer suggesting that these fractions have chemopreventive effects on DMBA induced oral carcinogenesis.</p>

Expression of survivin, caspase-3 in oral precancerous lesions and oral squamous-cell carcinoma / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the roles of surviving and caspase-3 in the development of oral cancer.</p><p><b>METHODS</b>Archival tissue sections of 17 oral squamous cell carcinoma (OSCC), 28 oral leukoplakia with dysplasia, 10 normal oral mucosa were obtained from Capital Medical University School of Stomatology for immunohistochemical staining of markers of survivin and caspase-3. The cell apoptosis was detected with terminal deoxynucleotidyl transferase-mediated nucleotide shift enzyme (TdT) mediated d-UTP end labeling (TUNEL). Positively stained cells were counted and analyzed statistically to determine potential relationship between survivin, caspase-3 and cell apoptosis.</p><p><b>RESULTS</b>The expression of survivin was faint or negative in normal epithelial cells. The average positive rate of survivin was (1.05 ± 1.21)% in control group and (21.89 ± 10.45)% in OSCC. Caspase-3 was expressed in all the normal mucosa,but it obviously down-regulated in dysplasia and OSCC. The apoptosis index (AI) decreased from (0.89 ± 0.46)% in normal mucosa to (0.21 ± 0.12)% in OSCC.</p><p><b>CONCLUSIONS</b>Both survivin and caspase-3 are associated with carcinogenesis of the oral mucosa. Survivin may restrain cell apoptosis by inhibiting caspase-3.</p>

Comparison of two nonalcoholic hepatocellular steatosis models / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare two models of nonalcoholic hepatocellular steatosis.</p><p><b>METHODS</b>HL-7702 cells were incubated with a mixture of of unsaturated oleate acid or 50% fetal bovine serum to induce fat-overloading. Significant fat accumulation was documented by Oil Red O staining , and intracellular triglyceride levels was detected by triglyceride enzymatic assay.</p><p><b>RESULTS</b>The results showed that both 0.5 mmol/ml oleate acid and 50% FBS were able to induce nonalcoholic hepatocellular steatosis.</p><p><b>CONCLUSION</b>A nonalcoholic hepatocellular steatosis was induced by 0.5 mmol/ml oleate acid.</p>