• Title/Summary/Keyword: adriamycin

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Effect of Dietary Vitamin A and E Peroxidative Deterioration of Heart in Adriamycin-Treated Rats (식이중의 Vitamin A와 E가 Adriamycin을 투여한 흰쥐의 심근손상의 원인인 과산화작용에 미치는 영향)

  • 정영아
    • Journal of Nutrition and Health
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    • v.25 no.5
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    • pp.379-388
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    • 1992
  • The present study was designed to evaluate the protective effects of dietary vitamin A or E. and of combination of vitamins A and E on peroxidative deterioration of heart in adriamycin-treated rats. Male Sprague-Dawley rats were assigned to 5 groups according to the dietary supplementation of vitamin A or E Except control rats a dose of 2mg ADR/kg of B. W was injected to these animals intraperitoneally on the same day every week. Adriamycin treatment significantly decreased the weight gain of experimental rats compared with that of control rats, But this decrement was not modified by dietary supplementation of vitamin A or E. Lipid peroxide values of plasma were elevated by ADR treatment. The combined use of ADR and dietary vitamin A or E significantly reduced these values, The interaction between vitamins A and E seemed to be present in the lipid peroxide value of plasma. Catalase and superoxide dismutase(SOD) activities in rat heart were decrased by ADR treatment but glutathione peroxidase(GSH-Px) activity was elevated. Dietary supplmen-tation of vitamin A or E enhanced the heart catalase and SOD activities. except only vitamin A-supplemented group. GSH-Px activity of rat heart tended to be decreased by dietary supple-mentation of vitamin A or E. With ADR treatment polyunsaturated fatty acids such as archido-nic acid(20:4) and docosahexaenoic acid(22:6) were decreased in rat heart. However dietary supplementation of vitamins A and E reduced this decrease. The retinol and tocopherol contents of rat plasma were decreased by ADR treatment. Dietary vitamin A or E influence vitamin A or E content of plasma. The interaction between dietary vitamins A and E was observed in vitamin A or E level of rat plasma.

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Local Irritation of DA-125 (DA-125의 국소자극성)

  • 안병옥;백남기;이순복;김원배;양중익;김부영;김대병;이종권
    • Biomolecules & Therapeutics
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    • v.1 no.1
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    • pp.20-25
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    • 1993
  • DA-125, a new anthracycline derivative, shows significant anticancer activities. We conducted a study to examine the local irritating effect of DA-125 using mice and rabbits. In the skin test in mice, intradermal injection of 0.4 mg of DA-125, compared to a dosage of 0.2 mg of adriamycin, had weak irritating potentials to induce skin ulceration and erythematous induration. A dosage of 0.6 mg of DA-125 produced similar degree of lesions in perivascular irritation model to that of 0.2 mg of adriamycin, but the healing time was shorter in the case of mice treated with DA-125. In ocular irritation study in rabbit, the highest M.O.I.(mean ocular irritation index) of 0.5% DA-125 solution was 0.67, therefore DA-125 could be considered as a practically non-irritating anticancer agent. These results suggest that substitution of DA-125 for Adriamycin would reduces the possibility of outbreaks of local irritation and the severity of the lesions.

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cis-Annonacin and (2,4)-cis-and trans-Isoannonacins: Cytotoxic Monotetrahydrofuran Annonaceous Acetogenins from the Seeds of Annona cherimolia

  • Woo, Mi-Hee;Chung, Soon-Ok;Kim, Dal-Hwan
    • Archives of Pharmacal Research
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    • v.22 no.5
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    • pp.524-528
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    • 1999
  • cis-Annonacin (1) and the mixture of (2,4)-cis-and trans-isoannonacins (2 and 3), three known mono-tetrahydrofuran annonaceous acetogenins, have been isolated form the seeds of Annona cherimolia by the use of the brine shrimp lethality test (BST) for bioactivity directed fractionation. Their structures were elucidated based on spectroscopic and chemical methods. 1 showed potent cytotoxicities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the pancreatic cell line (PaCa-2) at about 1,000 times the potency of adriamycin. The mixture of 2 and 3 is over 10,000 times cytotoxic as adriamycin in the pancreatic cell line (PaCa-2). All of the compounds are about 10 to 100 times as cytotoxic as adriamycin in the prostate cell line (PC-3).

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Cytotoxic Effect of Taxol on Malignant Bone Tumor Cell Lines (악성 골종양 세포주들에 대한 Taxol의 세포독성)

  • Shin, Duk-Seop;Kim, Se-Dong;Kim, Keon-Ho;Lee, Jong-Hyung;Kim, Seong-Yong;Kim, Jung-Hye
    • The Journal of the Korean bone and joint tumor society
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    • v.4 no.1
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    • pp.13-21
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    • 1998
  • Taxol, the extract from the Taxus brevifolia which is a Pacific yew tree has aroused the interest of the tumor investigators since the 1960s. As well, it is shown to have broad antitumor activity in preclinical experimental models. Its action mechanism is an anti-microtubule effect by duplication of tubulin. The most impressive antitumor activity of taxol has been observed in advanced ovarian cancer and metastatic breast cancer. The purpose of this study was to determine how taxol acts on malignant bone tumor cell lines, to compare its cytotoxic effect with those of other chemotherapeutic agents, and to ascertain the its combination effect with adriamycin. Cell lines used in this study were G-292(osteosarcoma, human), SaOS-2(osteosarcoma, primary, human), and HT-1080(fibrosarcoma, human). Methotrexate, adriamycin, cisplatinum, ifosfamide and taxol were used as testing chemotherapeutic agents and their maximum test concentration were $500{\mu}g/ml$, $200{\mu}g/ml$, $500{\mu}g/ml$, $1000{\mu}g/ml$, and $600{\mu}g/ml$, respectively. The media for cell culture was RPMI-1640 with 10% fetal bovine serum and gentamycin. The results were as follows. The $IC_{50}$ of methotrexate, ifosfamide, cisplatinum, adriamycin and Taxol in G-292 were $2.3{\times}10^{-1}{\mu}g/ml$, $8.0{\times}10^0{\mu}g/ml$, $3.5{\times}10^0{\mu}g/ml$, $9.8{\times}10^{-1}{\mu}g/ml$, $2.7{\times}10^{-2}{\mu}g/ml$ respectively, in SaOS-2 $3.5{\times}10^{-1}{\mu}g/ml$, $1.5{\times}10^1{\mu}g/ml$, $2.8{\times}10^0{\mu}g/ml$, $9.9{\times}10^{-2}{\mu}g/ml$, $1.0{\times}10^{-2}{\mu}g/ml$, respectively, in HT-1080 $4.2{\times}10^{-2}{\mu}g/ml$, $5.4{\times}10^1{\mu}g/ml$, $3.8{\times}10^0{\mu}g/ml$, $5.5{\times}10^{-3}{\mu}g/ml$, $1.1{\times}10^{-3}{\mu}g/ml$, respectively. In conclusion, taxol had very potent cytotoxic effect on the malignant bone tumor cell lines with adriamycin, and was more potent than methotrexate, cisplatinum and ifosfamide. There were synergistic antitumor effects on G-292 and SaOS-2 cell lines in combination test of taxol and adriamycin. From the above results, it would be estimated that taxol could be a new antitumor drug for the malignant bone tumors, providing measures against the side effects and followed by the clinical tests.

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Effects of Dietary Coenzyme $Q_10$ and Vitamin E on Lipid Peroxidation in Adriamycin-treated Rat (Coenzyme $Q_10$과 Vitamin E 첨가식이가 Adriamycin을 투여한 흰쥐의 체내 지질과산화에 미치는 영향)

  • 서정숙;양경미;정영아
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.20 no.4
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    • pp.320-328
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    • 1991
  • The present study was designed to evaluate the effects of dietary vitamin E and coenzyme $Q_{10}$ supplementation on adriamycin (ADR) -induced lipid petoxidation in rats. After feeding the experimental diets for e weeks. Ann treatment significantly decreased growth performance of rats. But this decrement was not modified by supplementation of vitamin E or coenzyme $Q_{10}$ . Lipid peroxide values of plasma and heart mitochondria were elevated by Ann treatment. But these values were significantly decreased according to vitamin E or coenzyme $Q_{10}$ supplementation. Adriamycin treatment elevated glutathione peroxidase (GSH-Px) activity of rats, but this increment was modified by vitamin E supplementation. There was a tendency of higher superoxide dismutase (SOD) activity in ADR-treated rats. However, vitamin E or coenzyme $Q_{10}$ administration reduced this enzyme activity. With ADR treatment, arachidonic acid (20 : 4) was greatly increased, but docosahexaenoic acid (22 : 6) was not detected. Arachidonic acid was decreased and docosahexaenoic acid increased by supplementation of higher level of vitamin E or coenzyme $Q_{10}$ . Present data showed that dietary vitamin E and coenzyme $Q_{10}$ influenced on ADR-induced lipid peroxidation in rats, and also the degree of antioxidative effect was greater in vitamin E-supplemented rats.

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Enhancement of Cytotoxicity by the Combination of Anticancer Drugs in Human Lung Adenocarcinoma Cell Line (PC-14) (폐암세포주 (PC-14)에서 복합항암제 처치시 암세포살해능의 증강에 관한 연구)

  • Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.525-533
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    • 1997
  • Background : No ideal combination chemotherapy for lung cancer has been established even though lots of combination anticancer chemotherapies have been tried. For the combination of anticancer drugs, the interaction of anticancer drugs is very important but unpredictable factor. In this experiment, we designed and tested new experiment to measure the interaction of two anticancer drugs using MIT assay in an attempt to predict clinical response of the combination regimen. Methods : With human lung adenocarcinoma cell line (PC-14), the cytotoxic effect of cisplatin, adriamycin, mitomycin C and etoposide were measured by in vitro chemosensitivity test (MIT assay). The combined cytotoxic effects of combination of two drugs were also measured in every combination of the drug concentrations and analyzed the interaction by Anava analysis of two way factorial design. Results : Four individual drugs showed cytotoxic effects on PC-14 by dose dependent fashion. Comparison of two drug combinations revealed that mitomycin C + cisplatin and adriamycin + cisplatin combinations showed stronger synergistic cytotoxic effects. Conclusion : From this experiment, we suggest two combinations of mitomycin C + cisplatin and adriamycin + cisplatin as chemotherapeutic regimens for unresectable non-small cell lung cancer. Furthermore, this experimental design could be applied to other types of cancer requiring combination anticancer chemotherapy.

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Effect of Bcl-2 on Apoptosis and Transcription Factor NF-κB Activation Induced by Adriamycin in Bladder Carcinoma BIU87 Cells

  • Zhang, Guo-Jun;Zhang, Zhe
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2387-2391
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    • 2013
  • Resistance to apoptosis is a major obstacle preventing effective therapy for malignancies. Bcl-2 plays a significant role in inhibiting apoptosis. We reconstructed a stable human Bcl-2 transfected cell line, BIU87-Bcl-2, that was derived from the transfection of human bladder carcinoma cell line BIU87 with a plasmid vector containing recombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. A cell line transfected with the plasmid alone [pcDNA3.1(+)-neo] was also established as a control. BIU87 and BIU87-neo proved sensitive to adriamycin induced apoptosis, while BIU87-Bcl-2 was more resistant. In view of the growing evidence that NF-${\kappa}B$ may play an important role in regulating apoptosis, we determined whether Bcl-2 could modulate the activity of NF-${\kappa}B$ in bladder carcinoma cells. Stimulation of BIU87, BIU87-neo and BIU87-Bcl-2 with ADR resulted in an increase expression of NF-${\kappa}B$ (p<0.001). The expression of NF-${\kappa}B$ in BIU87-Bcl-2 was higher than in the other two cases, with a concomitant reduction in the $I{\kappa}B{\kappa}$ protein level. These results suggest that the overexpression of Bcl-2 renders human bladder carcinoma cells resistant to adriamycin-induced cytotoxicity and there is a link between Bcl-2 and the NF-${\kappa}B$ signaling pathway in the suppression of apoptosis.

Signal Transduction of the Protective Effect of Insulin Like Growth Factor-1 on Adriamycin-Induced Apoptosis in Cardiac Muscle Cells

  • Chae, Han-Jung;Kim, Hyung-Ryong;Bae, Jee-hyeon;Chae, Soo-Uk;Ha, Ki-Chan;Chae, Soo-Wan
    • Archives of Pharmacal Research
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    • v.27 no.3
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    • pp.324-333
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    • 2004
  • To determine whether Insulin-like growth factor (IGF-I) treatment represents a potential means of enhancing the survival of cardiac muscle cells from adriamycin (ADR)-induced cell death, the present study examined the ability of IGF-I to prevent cell death. The study was performed utilising the embryonic, rat, cardiac muscle cell line, H9C2. Incubating cardiac muscle cells in the presence of adriamycin increased cell death, as determined by MTT assay and annexin V-positive cell number. The addition of 100 ng/mL IGF-I, in the presence of adriamycin, decreased apoptosis. The effect of IGF-I on phosphorylation of PI, a substrate of phosphatidylinositol 3-kinase (PI 3-kinase) or protein kinase B (AKT), was also examined in H9C2 cardiac muscle cells. IGF-I increased the phosphorylation of ERK 1 and 2 and $PKC{\;}{\zeta}{\;}kinase$. The use of inhibitors of PI 3-kinase (LY 294002), in the cell death assay, demonstrated partial abrogation of the protective effect of IGF-I. The MEK1 inhibitor-PD098059 and the PKC inhibitor-chelerythrine exhibited no effect on IGF-1-induced cell protection. In the regulatory subunit of PI3K-p85- dominant, negative plasmid-transfected cells, the IGF-1-induced protective effect was reversed. This data demonstrates that IGF-I protects cardiac muscle cells from ADR-induced cell death. Although IGF-I activates several signaling pathways that contribute to its protective effect in other cell types, only activation of PI 3-kinase contributes to this effect in H9C2 cardiac muscle cells.

Rhizoma Rehmanniae induced Apoptosis in Human Cervical Carcinoma HeLa Cells (생지황(生地黃)이 자궁경부암세포(子宮經部癌細胞)(HeLa cell)에 미치는 영향(影響))

  • Kim, Joo-Yeon;Jo, Ok-Hyon;Choe, Chang-Min;Cho, Han-Baek
    • The Journal of Korean Obstetrics and Gynecology
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    • v.19 no.1
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    • pp.69-80
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    • 2006
  • Purpose : This study is to evaluate the synergistic cytotoxicity of Rhizoma Rehmanniae(RR), in adriamycin-treated HeLa human cervical carcinoma cells. Methods : We culture HeLa cell which is human metrocarcinoma cell in D-MEM included 10% fetal bovine serum(Hyclone Laboratories) below $37^{\circ}C$, 5% $CO_2$. Then we observed apoptosis of log phage cell which is changed cultivation liquid 24 Hours periodically. Results : The combination of RR and adriamycin synergistically augmented the cytotoxicity of HeLa cells. The apoptotic cell death was accompanied by the activation of caspase-3 and -8 as well as cleavage of poly(ADP- ribose) polymerase (PARP) in HeLa cells. The co-treatment of RR with adriamycin didn't have any effect on either the expression of Bcl-2 or that of Bax. Interestingly, a synergistic increase in apoptosis by the combination of two drugs was accompanied by the enhancement of Pas and Fas ligand (FasL) expression in HeLa cells. Taken together, the combination of RR and adriamycin significantly augmented the apoptotic cytotoxicity of Fas-positive cells, such as HeLa cells. The pathway is not involved in mitochondria-dependent pathway. Conclusion : RR induces apoptosis in HeLa cells via p38 MAPK activation.

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Effects of dietary coenzyme Q10 on adriamycin-induced myocardial ultrastructural changes in rats (식이중의 Coenzyme Q10첨가가 Adriamycin을 투여한 흰쥐의 심근 미세구조에 미치는 영향)

  • Seo, Jung-Sook;Han, In-Kyu;Chung, Hyung-Jae
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.18 no.1
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    • pp.62-70
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    • 1989
  • The present study was designed to evaluate whether supplementation of dietary coenzyme Q10 protects the ADR-induced cardiotoxicity in rats. Experiment was undertaken under the condition of simultaneous adminstration of ADR and coenzyme Q10 for 4 weeks. Adriamycin treatment significantly decreased growth performance of rats. But this decrement was not modified by dietary supplementation of conzyme Q10. In the plasma creatine phosphokinase activity, there was no significant difference among experimental groups. Electron microscopic examination revealed a progression of myocardial lesions were dependent upon the level of ADR injection. The most frequently observed fine structural alterations in rat myocardium were mitochondrial swelling, dilation of the sarcoplasmic reticulum and the appearance of a perinuclear vacuolization. But these structural changes were somewhat lesser in defree by dietary supplementation of coenzyme Q10.

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