Apoptotic Effects of 6-Gingerol in Human Breast Cancer Cells

6-Gingerol exerts anti-tumor effects in various cancer cell models. We evaluated the effect of 6-gingerol on the growth of MCF-7 breast cancer cells and MCF-10A breast epithelial cells to determine whether any growth-inhibitory effects found were attributable to apoptosis, and to elucidate the underlying mechanism of action. 6-Gingerol inhibited the viability of both cell lines in a dose- and time-dependent manner; however, the degree of inhibition was greater in MCF-7 than MCF-10A cells. By flow cytometry, induction of dose- and time-dependent apoptosis was found, and the magnitude of apoptosis was also markedly greater in MCF-7 than MCF-10A cells. Expression of caspase-3 and poly (ADP-ribose) polymerase (PARP) was observed in MCF-7 cells treated with 6-gingerol, and further cleavage of PARP occurred in these cells. We suggest that 6-gingerol induces apoptosis in human breast cancer cells mainly by promoting caspase-3 expression and subsequent degradation of PARP.

Development Measures of the Journal of Korean Society for Clinical Pharmacology and Therapeutics

The Journal of Korean Society for Clinical Pharmacology and Therapeutics (JKSCPT) as a peer-reviewed semi-annual journal has published lots of clinical pharmacology articles of various fields since its first issue in May 1993. Particularly, a number of high-quality articles such as randomized controlled prospective clinical trials have been presented in this journal. The JKSCPT currently has been also indexed in Scopus, one of the famous international bibliographic databases, and the candidate journal accredited by the National Research Foundation of Korea. Although the JKSCPT has accumulated outstanding achievements as the specialized journal for clinical pharmacology in Korea, it is also true that there are many problems to be solved in order to be a more internationally recognized journal. The methods to analyze the status of a journal for the academic society were first suggested in this article. The SWOT analysis on the current status of the JKSCPT was done for establishing future development strategies. Making references to these analyzing methods of a journal and SWOT analysis, numerous problems and the suggestions for the development of the JKSCPT were presented in detail. The future model of the journal for the academic society was also briefly discussed.

An Analysis of Articles Published in the Journal of Korean Society for Clinical Pharmacology and Therapeutics

BACKGROUND: To grasp the status and future directions, an analysis was done on the articles published in the Journal of Korean Society for Clinical Pharmacology and Therapeutics during recent 19 years. METHODS: All the articles published from 1993 through 2011 were retrospectively analyzed. The number of articles and their language distribution were assessed. The articles were classified according to research types. Authors' affiliations and research fields of articles were also analyzed. RESULTS: The Journal of Korean Society for Clinical Pharmacology and Therapeutics as a semi-annual journal published 353 articles (3,659 pages in total) since its first issue in May 1993. A total of 37 issues were published with the average of 10.1 articles per issue. Most articles were written in the Korean language (94.9 %). In publication type of articles, 13.2 % were review articles, 66.7 % original articles, 18.0 % symposium articles, and the rest other types. In affiliation analysis, most authors were from the academia (91.0 %), next from the industry (5.8 %), and thirdly from the authority (2.3 %). The research field dealt with the highest (28.0 %) was Pharmockinetics/Pharmacodynamics/Pharmacometrics (PPP), core of clinical pharmacology. Many articles in PPP field contained the randomized controlled prospective clinical trials, which are the highest level of evidence, indicating high quality of articles. CONCLUSION: These results suggest that the Journal of Korean Society for Clinical Pharmacology and Therapeutics reflects typically the specialized journal for clinical pharmacology. The internationalization efforts for our journal is also required.

Inhibitory Effects of 6-Gingerol on Cytochrome P450 in Human Liver Microsomes

No abstract available.

Apoptotic Effects of 6-Gingerol in LNCaP Human Prostate Cancer Cells

OBJECTIVE: 6-Gingerol, one component of ginger (Zingiber officinale) compound, has been known to possess anti-inflammatory, analgesic, anti-emetic, and anti-cancer effects. In this study, the apoptotic ability of 6-gingerol was investigated in human prostate cancer cells. METHODS: 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide (MTT) assay, flow cytometry, and western blot analysis were done in LNCaP human prostate cancer cell lines treated with the various doses of 6-gingerol for the different durations of drug exposure. RESULTS: 6-Gingerol in doses ranging from 100 to 300 microM induced dose- and time-dependent inhibition of cell viability in prostate cancer cells by using MTT assay. Maximal inhibition of cell viability was observed at 300 microM of 6-gingerol for 48 hours treatment in LNCaP cells. 6-Gingerol at the dose of 100 microM did not produce any significant change in apoptotic cells in flow cytometry analysis. However, significant increase in sub-G0/G1 phase was observed in cells treated with 200 and 300 microM of 6-gingerol. Any significant cell cycle arrest was not induced by 6-gingerol. In western blotting analysis, expression of caspase-3 was not evident in cells treated with 6-gingerol for 24 hours. However, 48 hours treatment with 6-gingerol altered the expression of caspase-3 in LNCaP cells. Expression of cleaved poly showed the dose-dependent fashion in both 24 hours and 48 hours treatment of 6-gingerol. CONCLUSION: These observations suggest that 6-gingerol may induce apoptosis in LNCaP human prostate cancer cells.

Studies on the Mechanism of Renal Action of Centrally-administered TFMPP in Rabbits / 대한신장학회잡지

It has been known that central tryptaminergic system is closely related with the regulation of renal function, and that central 5-HT1 receptors mediate diuresis and natriuresis, whereas central 5-HT2 and 5-HT3 receptors mediate antidiuresis and antinatriuresis. Among many subtypes of 5-HT1 receptors, central 5-HT1A subtype has been suggested to exert diuretic and natriuretic effets. Further, it was recently observed that TFMPP, 5-HT1B agonist, elicited profound diuresis and natriuresis when administered intracerebroventricularly(icv). Present study is therefore undertaken to delineate the mechanism involved in the natriuresis and diuresis induced by icv TFMPP, employing the denervated and vagotomized rabbits. The influence of icv TFMPP on the plasma level of ANP was also observed. TFMPP 250 microgram/kg icv produced marked diuresis and natriuresis. Renal hemodynamics showed significant increase only in the first 10-min period after administration and thereafter tended to recover. However, natriuretic action lasted even after the increased renal hemodynamics returned to the control level, suggesting the decreased Na reabsorption in the tubules by humoral natriuretic factors. Systemic blood pressure transiently increased. In rabbits in which one kidney is denervated, with the contralateral intact as the control kidney, the denervated kidney also responded with natriuresis and diuresis like that of the normal rabbit. The contralateral kidney responded with typical diuretic and natriuretic effects, along with the marked increased of renal hemodynamics. The plasma ANP, one of humoral natriuretic factors, increased after administration of icv TFMPP, peaking at about 15min. In bilaterally vagotomized rabbits, the natriuretic and diuretic effects produced by icv TFMPP were greater than that of the normal rabbits. These observations suggest that the natriuresis and diuresis elicited by icv TFMPP result from the inhibition of tubular Na reabsorption mainly through mediation of ANP. It has been also suggested that vagus nerve might exert inhibitory influence on the diuretic action of icv TFMPP, because the renal effects was augmented in the vagotomized rabbits.

Influence of Intracerebroventricular Kallikrein and Lys-bradykinin on the Rabbit Renal Function / 대한신장학회잡지

The renal function is under regulatory influence of central nervous system, in which various neurotransmitter and neuromodulator systems take part, and it has been known that kallikrein-kininogen- kinin system exists also in the brain, but its physiological role remains to be explored. This study was, therefore, undertaken to delineate the possible role of central kinin system in the regulation of renal function. Kallikrein given into a lateral ventricle(icv) of rabbit brain in doses ranging from 3 to 30 microgram/kg icv elicited increases in Na excretion and the fraction of filtered sodium excreted(FENa), as well as in urine flow rate. K excretion, however, did not parallel the Na excretion, but tended to decrease when the natriuresis reached its peak. Renal blood flow and glomerular filtration did not significantly change. Neither did free water reabsorption significantly change, but tended to decrease. The systemic blood pressure slightly increased. When 30 microgram/kg kallikrein was given intravenously, all the parameters of renal function and systemic blood pressure did not show any increase but decrease, primarily by decreased renal hemodynamics, resulting from transient hypotension. In experiments in which the plasma ANP was measured, the ANP level markedly increased, reaching more than 5 times the control value 25min after 30 microgram/kg icv, and lasting until the end of the experiment at 80min. The renal nerve activity increased with kallikrein, 30 microgram/kg icv, peaking at 1 min but it remained slightly increased until about 40 min, and then slightly declined. This indicates that the increased renal nerve activity may have antagonized or ameliorated the natriuretic effect of icv kallikrein. Lys-bradykinin(kallidin), a cleavage product from kallidinogen by kallikrein, when given icv in doses of 0.3 to 30 microgram/kg also produced increased Na excretion and diuresis. When CHA, a kallikrein inhibitor, was given icv in doses of 3-30 microgram/kg, elicited antidiuresis and antinatriuresis. However, pretreatment with CHA tended slightly to suppress the kallikrein effect. These results indicate that the central kallikrein- kinin system is involved in the central regulation of renal function, the activation of the system in the CNS resulting in increased natriuresis and diuresis, which are related to increased plasma ANP level, with the possible antagonistic effects of increased renal nerve activity.

Renal functional responses to a centrally-administered 5-HT-1A agonist in the anesthetized rabbits

Central tryptaminergic system has been shown to play an important role in the regulation of renal function: 5-HT-1 (5-hydroxytryptamine-1) receptors might seem to mediate the diuresis and natriuresis, whereas the 5-HT-2 and 5-HT-3 receptors mediate the antidiuretic and antinatriuretic effects. This study attempted to delineate the role of central 5-HT-1A subtype in the regulation of rabbit renal function by observing the renal effects of intracerebroventricularly(icv)-administered PAPP (p-aminophenylethyl-m-trifluoromethylphenyl piperazine, LY165163), a selective agonist of 5-HT-1A receptors. PAPP in doses ranging from 40 to 350 microgram/kg icv induced significantly diuresis, natriuresis, and kaliuresis, along with increased renal perfusion and glomerular filtration. Systemic blood pressure was also increased. Free water reabsorption (T-cH-2O), a measure of ADH (antidiuretic hormone) secretion, was increased also. Intravenous 350 microgram/kg of PAPP elicited antidiuresis and antinatriuresis together with decreased blood pressure, thus indicating that the effects of icv PAPP were brought about through the central mechanisms, not by direct peripheral effects of the drug on kidney. Ketanserin, a selective 5-HT-2 antagonist, 40 microgram/kg icv, did not affect the renal effects of the icv PAPP. Methysergide, a non-selective 5-HT-1 antagonist, also did not block the renal functional responses by the icv PAPP. NAN-190, a 5-HT-1A antagonist, also did not antagonized the renal action of the icv PAPP. However the increased free water reabsorption was abolished by both methysergide or ketanserin pretreatment. The increments of blood pressure by icv PAPP was blocked only by NAN-190 pretreatment. These observations suggest that the central 5-HT-1A receptor might be involved in the central regulation of rabbit renal function by exerting the diuretic and natriuretic influences.