• Title/Summary/Keyword: chemotherapeutic agent

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Antioxidant and Apoptotic Effects of an Aqueous Extract of Urtica dioica on the MCF-7 Human Breast Cancer Cell Line

  • Fattahi, Sadegh;Ardekani, Ali Motevalizadeh;Zabihi, Ebrahim;Abedian, Zeinab;Mostafazadeh, Amrollah;Pourbagher, Roghayeh;Akhavan-Niaki, Haleh
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5317-5323
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    • 2013
  • Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of $r^2$=0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an $IC_{50}$ value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.

The Effect of the Periods of Bed Rest on the Postlumbar Puncture Headache in Pediatric Oncology Patients (소아혈액 종양환자의 요추천자 후 침상안정시간이 천자 후 두통에 미치는 영향)

  • Kim, Yeong-Mi
    • The Korean Nurse
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    • v.36 no.2
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    • pp.73-83
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    • 1997
  • Bed rest is recommended to prevent postlumbar puncture headaches(PLPHA), but the period of bed rest varies in the literature from 6 hours to 24 hours. In clinical practice the period of bed rest varies but nursing methods for adults and children have little difference. In Seoul National University Hospital, children have been given at least 6 hours bed rest after a lumbar puncture. Pediatric oncology patients require a lumbar puncture for an initial diagnosis, follow up treatment or administration of chemotherapeutic agent. But it is difficult for young children to lie supine or to refrain from their usual activities in any way, and unpleasant problems related to a shortage of beds often occurs during discharge or in an outpatient setting. The purpose of this study is to substantiate the preventive effect of PLPHA by the period of bed rest, to identify the other factors that influence PLPHA, and to use the nursing methods proper to children. The subjects were 65 children, ages 1-17, undergoing treatment in the children's cancer center at SNUCH during the period June 1, 1995, to Aug. 31, 1995. The team nurses asked questions about PLPHA of the parents and children in order to fill out a questionnaire. The data were evaluated by percent, t-test, Chi-square test and Mann-Whitney U test. Result; 1. There was no significant difference relating the bed rest time spent to the occurrence of postspinal headaches (t-test). 2. There was a significant risk of PLPHA in the children who were irritable before procedure and/or had experienced previous PLPHA(p<0.05, ${x^2}-test$). 3. The following factors were not found to be associated with increased risk of PLPHA: previous puncture experience, giving analgesics, the choice of puncturist, inpatient/outpatient status, gauge of needle, purpose, the amount of CSF removed, gender, diagnosis, the number of peripheral WBCs, previous lumbago experience after LP, position after bed rest, age, the number of aural puncture at the time. A longer period of bed rest is unlikely to be more effective to prevent PLPHA and seems impractical. A shorter period will save time and effort. Perhaps it will also allay some of the fears which surround LP. So 1 hour bed rest after LP is suggested and nursing methods for emotional support should be investigated to reduce PLPH.

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Effect of the Paclitaxel and Radiation in the Mucosa of the Small Bowel of Rat (흰쥐의 소장점막에 Paclitaxel(Taxol)과 방사선조사의 효과)

  • Lee Kyung-Ja
    • Radiation Oncology Journal
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    • v.14 no.4
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    • pp.255-264
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    • 1996
  • Purpose : Paclitaxel is a chemotherapeutic agent with potent microtubule stabilizing activity that arrests cell cycle in $G_2$-M Because $G_2$-M is the most radiosensitive Phase of the cell cycle, paclitaxel has potential as a cell cycle- specific radiosensitizer. This study was designed to investigate the ability of paclitaxel to increase the radiotoxicity in normal small bowel mucosa of the rat. materials and Methods : A sigle intraperitoneal infusion of paclitaxel (10mg/kg), and a single irradiation(8 Gy, x-ray) to the whole abdomen and combination of radiation(8 Gr, x-ray) 24 hours after paclitaxel infusion in the rats were done. The changes of jejunal mucosa, and kinetics of mitotic arrest and apoptosis in the jejunal crypt were defined at 6 hours - 5 days after each treatment histologically. Results : Paclitaxel blocked jejunal crypt cell in mitosis and induced minmal apoptosis. Mitotic arrest by paclitaxel was peaked at 6 hours after infusion and returned to normal by 24 hours. Radiation induced apoptosis and peaked at 6 hours and returned to normal by 24 hours. Combination of paclitaxel and radiation blocked crypt cell in mitosis at 3 days and induced apoptosis slightly at 6 hours and 24 hours and returned to normal by 3 days. The incidence of apoptosis in combined group at 6 hours was slightly higher than normal control but significantly lower than radiation alone group. The major changes of jejunal mucosa were nuclear vesicle and atypia which were appeared at 6 hours - 3 days and returned to normal by 5 days The degree of the mucosal changes are not different in 3 groups except for absence of inflmmatory reaction in radiation group. Conclusion : Mitotic arrest by paclitaxel was peaked at 6 hours and returned to normal by 24 hours and paclitaxel induced minimal apoptosis. Radiation induced apoptosis, peaked at 6 hours and returned to normal by 24 hours. Radiation-induced apoptosis was less in combined group which suggested that paclitaxel have a radioprotective effect when radiation was given 24 hours after paclitaxel infusion.

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Induction of Apoptosis by Pachymic Acid in T24 Human Bladder Cancer Cells (T24 인체방광암 세포에서 pachymic acid에 의한 apoptosis 유발)

  • Jeong, Jin-Woo;Baek, Jun Young;Kim, Kwang Dong;Choi, Yung Hyun;Lee, Jae-Dong
    • Journal of Life Science
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    • v.25 no.1
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    • pp.93-100
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    • 2015
  • Pachymic acid (PA) is a lanostane-type triterpenoid derived from the Poria cocos mushroom. Several beneficial biological features of PA provide medicine with a wide variety of valuable effects, such as anticancer and anti-inflammatory activity; it also has antioxidant effects against oxidative stress. Nonetheless, the biological properties and mechanisms that produce this anti-cancer action of PA remain largely undetermined. In this study, we investigated the pro-apoptotic effects of PA in T24 human bladder cancer cells. It was found that PA could inhibit the cell growth of T24 cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies and chromatin condensation and accumulation of cells in the sub-G1 phase. The induction of apoptotic cell death by PA was connected with an up-regulation of pro-apoptotic Bax and Bad protein expression and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL proteins, and inhibition of apoptosis family proteins. In addition, apoptosis-inducing concentrations of PA induced the activation of caspase-9, an initiator caspase of the mitochondrial-mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. PA also induced apoptosis via a death receptor-mediated extrinsic pathway by caspase-8 activation, resulting in the truncation of Bid and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. Taken together, the present results suggest that PA may be a potential chemotherapeutic agent for the control of human bladder cancer cells.

Anti-proliferative Effects of the Isothiocyanate Sulforaphane on the Growth of Human Cervical Carcinoma HeLa Cells (Sulforaphane에 의한 HeLa 인체자궁경부함세포의 증식 억제 기전 연구)

  • Park Soung Young;Bae Song-Ja;Choi Yung Hyun
    • Journal of Life Science
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    • v.15 no.3 s.70
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    • pp.397-405
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    • 2005
  • Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human cancer cells, however its molecular mechanisms are poorly understood. In the present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human cervical carcinoma HeLa cells. Treatment of HeLa cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells (9.83 fold of control). This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of cyclin A and cyclin-dependent kinase (Cdk)4 protein and concomitant induction of Cdc2, Cdk inhibitor p16 and p21. However, sulforaphane did not affect the levels of cyelooxygenases and telomere-regulatory gene products. Although further studies are needed, the present work suggests that sulforaphane may be a potential chemoprevetive/ chemotherapeutic agent for the treatment of human cancer cells.

NECROSIS OF ALVEOLAR BONE BY FORMOCRESOL : CASE REPORT (Formocresol에 의한 치조골 괴사의 치험례)

  • Park, Cheol-Hong;Lee, Chang-Seop;Lee, Sang-Ho;Lee, Nan-Young
    • Journal of the korean academy of Pediatric Dentistry
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    • v.32 no.4
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    • pp.657-661
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    • 2005
  • Various chemotherapeutic agents have been recommended for pulpotomy of primary teeth, and there are formocresol, ferric sulfate, and calcium hydroxide. Of those, formocresol has fixation effect of pulp tissue and high clinical success rate, so it is most commonly used agent. But formocresol has strong cytotoxic effects, thus many articles reported displacement and loss of permanent successor, amelogenesis imperfecta, mutation by general absorption, possibility of cancer induction. Recently, it has been reported that leakage by imperfect temporary sealing when FC-soaked cotton was inserted into the root canal caused necrosis of surrounding tissues. and that necrosis of alveolar bone related to the use of excessive formocresol. In this case, 2nd primary molar of upper left jaw was treated using formocresol in local clinic, but extracted because of lasting pain. Furthermore, symptoms didn't disappear so patient was refered to us. The patient was 8-year-old male, had foul odor from oral cavity and circular alveolar bone necrosis around the permanent successor' crown. Thus sequestrectomy was operated and observed through 19 months after operation, we found normal root development of permanent successor but no complete regeneration of alveolar bone defect and attached gingiva. Lesion of periodontal tissues by formocresol is irreversible, so we have to confirm the indication in using formocresol and pay attention to complete temporary sealing.

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Antitumor Activity of LB42907, a Potent and Selective Farnesyltransferase Inhibitor: Synergistic Effect in Combination with Other Anticancer Drugs

  • Park, Ji-Hyun;Koo, Sun-Young;Kim, Dong-Myung;Kim, Kwi-Hwa;Jeong, Shin-Wu;Chung, Hyun-Ho;Cho, Heung-Soo;Park, Joong-Hoon;Yim, Hyeon-Joo;Lee, Jin-Ho;Koh, Jong-Sung;Kim, Se-Mi
    • Bulletin of the Korean Chemical Society
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    • v.29 no.7
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    • pp.1303-1310
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    • 2008
  • Inhibitors of farnesyltransferase (FT), a key enzyme in the post-translational modifications of Ras proteins, have been extensively studied as novel anticancer agents in the preclinical stages, some of which are currently in clinical development. Previously, it has been reported that a novel FT inhibitor LB42907 inhibits Ras farnesylation in the nanomolar range in vitro. The aim of this study was to assess the antitumor efficacy of LB42907 in vitro and in vivo. Anchorage-independent growth of various human tumor cell lines was potently inhibited by treatment with LB42907, comparable to other FT inhibitors in clinical development. In the nude mouse, oral administration of LB42907 demonstrated potent antitumor activity in several human tumor xenograft models including bladder, lung and pancreas origin. Interestingly, significant tumor regression in EJ (bladder) and A549 (lung) xenografts was induced by LB42907 treatment. The effectiveness of LB42907 was also investigated in simultaneous combination with paclitaxel, vincristine, cisplatin or gemcitabine against NCI-H460, A549, and HCT116 cells in vitro using median-effect analysis. LB42907 markedly synergized with most anticancer drugs tested in this study in NCI-H460 cell. In contrast, LB42907 displayed antagonism or partial synergism with these drugs in A549 and HCT116 cells, depending on the class of combined drugs and/ or the level of cytotoxicity. Our results demonstrate that LB42907 is an effective antitumor agent in vitro and in vivo and combination of LB42907 with other chemotherapeutic drugs results in synergistic or antagonistic effects mainly in a cell line-dependent manner. Further preclinical study is warranted.

Apoptotic Cell Death of Human Leukemia U937 Cells by Essential Oil purified from Schisandrae Semen (오미자 종자 정유에 의한 인체백혈병 U937 세포의 apoptosis 유도)

  • Choi, Yung Hyun
    • Journal of Life Science
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    • v.25 no.2
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    • pp.249-255
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    • 2015
  • Schisandrae fructus [Schizandra chinensis (Turcz.) Baillon] is a medicinal herb widely used for treating various inflammatory and immune diseases in East Asian countries. The Schisandrae Semen essential oil (SSeo) from this plant has pharmacological activities, including antioxidant, antimicrobial, and antitumoral activities. Nevertheless, the biological activities and underlying molecular mechanisms of the potential anti-cancer effects of this oil remain unclear. In the present study, we investigated the potential inhibition of apoptosis signaling pathways by SSeo in human leukemia U937 cells and evaluated the underlying molecular mechanism. Exposure to SSeo resulted in a concentration-dependent growth inhibition due to apoptosis, which was verified by DNA fragmentation, the presence of apoptotic bodies, and an increase in the sub-G1 ratio. Induction of apoptotic cell death by SSeo was correlated with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family (including X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and surviving) and anti-apoptotic Bcl-2, and with up-regulation of death receptor (DR) 4 and DR5, depending on dosage. SSeo treatment also induced Bid truncation, mitochondrial dysfunction, proteolytic activation of caspase-3, -8 and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase. Taken together, these findings suggest that SSeo may be a potential chemotherapeutic agent for use in the control of human leukemia cells. Further studies are needed to identify its active compounds.

Induction of Apoptosis by Ethanol Extract of Scutellaria baicalensis in Renal ell Carcinoma Caki-1 Cells (황금(黃芩) 에탄올 추출물에 의한 인체 신세포암 Caki-1 세포의 자가세포사멸 유도)

  • Hwang, Won Deok;Im, Yong-Gyun;Son, Byoung Yil;Park, Cheol;Park, Dong Il;Choi, Yung Hyun
    • Journal of Life Science
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    • v.23 no.4
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    • pp.518-528
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    • 2013
  • Scutellaria baicalensis, belonging to the family Labiatae, is widely distributed in Korea, China, Mongolia, and eastern Siberia. It has been used in traditional medicine for various diseases, such as dysentery, pyrexia, jaundice, and carbuncles. In addition, S. baicalensis is reported to possess various beneficial pharmacological activities, including anti-inflammatory, antidiabetic, antiviral, antihypertension, antioxidant, and anticancer effects. However, the molecular mechanisms of its anticancer activity have not been clearly elucidated. In the present study, we investigated the proapoptotic effects of ethanol extract of S. baicalensis (EESB) on human renal cell carcinoma Caki-1 cells. The anti-proliferative activity of EESB was associated with apoptosis induction, which was associated with the up-regulation of death receptor 4, the Fas ligand, and Bax and the down-regulation of Bid, XIAP, and cIAP-1 proteins. EESB treatment also induced mitochondrial dysfunction, proteolytic activation of caspase-3, -8, and -9 and degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase, ${\beta}$-catenin, and phospholipase C-${\gamma}1$. However, pretreatment of a pan-caspase inhibitor, z-VAD-fmk, significantly attenuated the EESB-induced apoptosis. Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent. Further studies will be needed to identify the active compounds that confer the anticancer activity of S. baicalensis.

Induction of Cell Cycle Arrest at G2/M phase by Ethanol Extract of Scutellaria baicalensis in Human Renal Cell Carcinoma Caki-1 Cells (황금 에탄올 추출물에 의한 인간 신장암 세포주 Caki-1의 G2/M arrest 유발)

  • Park, Dong-Il;Jeong, Jin-Woo;Park, Cheol;Hong, Su-Hyun;Shin, Soon-Shik;Choi, Sung-Hyun;Choi, Yung-Hyun
    • Herbal Formula Science
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    • v.23 no.2
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    • pp.199-208
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    • 2015
  • Objectives : In the present study, we investigated the effects of ethanol extract of Scutellaria baicalensis (EESB) on the progression of cell cycle in human renal cell carcinoma Caki-1 cells. Methods : The effects of EESB on cell growth and apoptosis induction were evaluated by trypan blue dye exclusion assay and flow cytometry, respectively. The mRNA and protein levels were determined by Western blot analysis and reverse transcription-polymerase chain reaction, respectively. Results : It was found that EESB treatment on Caki-1 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by Annexin V-FITC staining. The flow cytometric analysis indicated that EESB resulted in G2/M arrest in cell cycle progression which was associated with the down-regulation of cyclin A expression. Our results also revealed that treatment with EESB increased the mRNA and proteins expression of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), without any noticeable changes in cyclin B1, Cdk2 and Cdc2. In addition, the incubation of cells with EESB resulted in a significant increase in the binding of p21 and Cdk2 and Cdc2. These findings suggest that EESB-induced G2/M arrest and apoptosis in Caki-1 cells is mediated through the p53-mediated upregulation of Cdk inhibitor p21. Conclusions : Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent and further studies will be needed to identify the biological active compounds that confer the anti-cancer activity of S. baicalensis.