• Journal of Korean Academy of Nursing
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• v.44 no.4
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• pp.371-380
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• 2014

Purpose: The purpose of this study was to examine the effects of Cu/Zn SOD on reduction of hindlimb muscular atrophy induced by cisplatin in rats. Methods: Forty-two rats were assigned to three groups; control group, Cisplatin (CDDP) group and cisplatin with Cu/Zn SOD (CDDP-SOD) group. At day 35 hindlimb muscles were dissected. Food intake, activity, withdrawal threshold, muscle weight, and Type I, II fiber cross-sectional area (CSA) of dissected muscles were measured. Relative SOD activity and expression of MHC and phosphorylated Akt, ERK were measured after dissection. Results: Muscle weight and Type I, II fiber CSA of hindlimb muscles in the CDDP group were significantly less than the control group. Muscle weight and Type I, II fiber CSA of hindlimb muscles, food intake, activity, and withdrawal thresholds of the CDDP-SOD group were significantly greater than the CDDP group. There were no significant differences in relative SOD activities of hindlimb muscles between the CDDP-SOD and CDDP groups. MHC expression and phosphorylated Akt, ERK of hindlimb muscles in the CDDP-SOD group were significantly greater than the CDDP group. Conclusion: Cu/Zn SOD attenuates hindlimb muscular atrophy induced by cisplatin through increased food intake and activity. Increment of phosphorylated Akt, ERK may relate to attenuation of hindlimb muscular atrophy.

• Journal of Korean Biological Nursing Science
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• v.14 no.1
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• pp.49-56
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• 2012

Purpose: The purpose of this study was to compare the effects of anorexia induced by consecutive low-dose and high-dose of cisplatin (CDDP) on the hindlimb muscles of rats. Methods: Male Sprague-Dawley rats were assigned to three groups: Control group (C) received a saline (the same dose and duration as the low CDDP group), the high-dose cisplatin (High CDDP) group received a single 5 mg/kg dose of cisplatin, the consecutive low-dose cisplatin (Low CDDP) group had 1 mg/kg of cisplatin administered for five consecutive days. On the 8th day the soleus and gastrocnemius muscles were dissected. Body weight, food intake, activity, muscle weight, Type I, II fiber cross-sectional area (CSA) of the dissected muscles were measured. Results: Body weight, food intake, muscle weight and Type I, II fiber CSA of the High CDDP and Low CDDP groups were significantly less than the C group. The High CDDP group showed significant decreases, compared to the Low CDDP group, in body weight, food intake, activity score, muscle weight and Type I, II fiber CSA. Conclusion: Hindlimb muscle atrophy occurs due to anorexia induced by both consecutive low-dose and high-dose cisplatin. The muscle atrophy induced by consecutive low-dose cisplatin is less apparent than high-dose cisplatin.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.85-91
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• 2004

In all attempt to elucidate the role of apoptosis in drug resistance, cisplatin-resistant human chronic myelogenous leukemia (CML) K562 cells (K562/CDDP) were established and compared with drug sensitive parent cells (K562) in the induction of apoptosis. K562/CDDP cells were 5-fold more resistant to cisplatin compared to K562 cells. In addition, K562/CDDP cells were significantly more resistant to apoptois as judged by DNA fragmentation and DAPI staining. K562/CDDP cells exhibited decreased proleolytic activity of caspase-3 and this was further demonstrated by decreased cleavage of its substrate poly (ADP-ribose) polymerase (PARR- Western blot analysis showed that K562/CDDP cells had longer sustained levels of BCL-$X_L$ whereas no difference was noted in the level of Bcl-2. the translocation of Bax to mitochondria was significantly delayed in K562/CDDP cells. These results suggest that the reduced translocation of Bax and the sustained expression of BCL-$X_L$ may cause resistance to apoptosis through prevention of mitochondria release of cytochrome c, which subsequently induces reduction of caspase-3 activity and that this response is partly responsible for the acquired resistance to cisplatin ill K562 cells.

• Biomedical Science Letters
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• v.14 no.2
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• pp.83-89
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• 2008

We have compared the antitumor effect of photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) as the photosensitizer, combined with cisplatin (CDDP) on AMC-HN3 human squamous cell carcinoma. AMC-HN3 cells were cultured and then incubated with various concentrations of CDDP and ALA. 632 nm diode laser was given at $6.0J/cm^2$ followed by incubation for 24 hours. The evaluation of cell viability was done by MTT assay. In vivo CDDP was injected intraperitoneally 24 hours prior to PDT. The anti-tumor effects of each treatment were measured by tumor volume change. Cell viability were 44.29% for the cisplatin-mediated chemotherapy group $(6.25{\mu}g/ml)$, 77.22% for ALA-PDT group, and 15.06% for the Combination therapy group. In vivo, the antitumor effect of photodynamic therapy was enhanced by combination of Cisplatin-mediated chemotherapy. Photodynamic therapy combined with administration of Cisplatin appears to enhance antitumor effect and to be a useful treatment modality.

• BMB Reports
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• v.44 no.3
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• pp.211-216
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• 2011

Vitamin C (VC) is an important antioxidant and enzyme co-factor that works by stimulating the immune system and protecting against infections. It is well known that melanoma cells are more susceptible to VC than any other tumor cells. However, the role of VC in the treatment of colon cancer has not been studied. Cisplatin (CDDP) is a DNA damaging agent and is widely used for treating cancer, while the role of p53 in CDDP-induced cell death has been stressed. Using cell growth assays, morphological methods, Western blotting, flow cytometry, and DNA fragmentation analysis, we measured the expression of p53 level involved in the effect of VC on CDDP-induced apoptosis of HCT116, a human colon cancer cell line. CDDP plus VC treatment resulted in significantly increased apoptosis along with upregulation of p53 compared to untreated cells and/or CDDP-treated cells. These results suggest that VC enhanced CDDP sensitivity and apoptosis via upregulation of p53.

• Applied Microscopy
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• v.40 no.3
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• pp.133-138
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• 2010

Mountain ginseng is a perennial crop rarely found in the deep mountains of Korea. The medicinal effect of the mountain ginseng is well known as a panacea in traditional Chinese medicine for a long time. But scientific studies to elucidate the medicinal effect of the mountain ginseng have never been made on account of lack of sample. Recently an improved method of adventitious root culture system through the use of bioreactor has been developed in Panax ginseng that seems to be a reliable way of commercialization of root derived secondary metabolites. This experiment was conducted to evaluated chemotherapeutic effect against human cervical cancer cells by cisplatin (CDDP) and extract of tissue cultured mountain ginseng (ETCMG). CDDP and ETCMG-induced apoptotic cell death in human cervical cancer cell line, HeLa was confirmed by the analysis of cell growth, morphological changes, DNA fragmentation, flow cytometry showed that ETCMG is an inducer of apoptosis and synergizes with CDDP. These results suggest that ETCMG present evidence of anticancer effect and could have a possibly natural therapeutic potential in cervical cancer patients.

• BMB Reports
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• v.39 no.6
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• pp.656-661
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• 2006

Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP -induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6877-6882
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• 2015

Background: Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer. We investigated the effect of selenium (Se) with high dose vitamin E (VE) administration to prevent CDDP-induced nephrotoxicity in rats. Materials and Methods: In this study, 40 female Wistar rats were randomly divided into five equal groups. The first group, which served as the control, was administered physiological saline (2.5 cc/day, 5 days) intraperitoneally (IP), while group A was administered cisplatin (6 mg/kg BW/ single dose) plus physiological saline IP. Groups B, C, D received IP five doses of Se (1.5 mg/kg BW), and a high dose of VE (1000 mg/kg BW) (Se-VE) in combination before, simultaneously, and after CDDP, respectively. The rats were sacrificed five days after CDDP administration. Plasma malondialdehide (MDA), glutathione peroxidase (GSH-Px), reduced glutathione (GSH), catalase, urea, creatinine levels, renal histopathological changes were measured. Results: The histopathological injury score, plasma levels of MDA, urea, creatinine were found to increase in group A compared to the control (p<0.05), while plasma levels of GSH-Px, GSH and catalase decreased (p<0.05). In contrast, plasma levels of MDA decreased (p<0.05) in groups B, C, D, which were treated with Se- VE, whereas levels of GSH-Px, GSH were found to increase only for group D (p<0.05). Plasma urea, creatinine levels improved in the treatment groups compared to group A (p<0.001). Histopathological changes caused by CDDP were also significantly improved after Se-VE treatment (p<0.05). Conclusions: Oxidative stress increases with CDDP-induced nephrotoxicity in rats. Se-VE supplementation might thus play a role in the prevention of CDDP-induced nephrotoxicity in patients.

• Molecules and Cells
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• v.37 no.9
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• pp.699-704
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• 2014

Themetastasis-associated gene 1 (MTA1) oncogene hasbeen suggested to be involved in the regulation of cancer progression. However, there is still no direct evidence that MTA1 regulates cisplatin (CDDP) resistance, as well as cancer stem cell properties. In this study, we found that MTA1 was enriched in CNE1/CDDP cells. Knock down of MTA1 in CNE1/CDDP cells reversed CSCs properties and CDDP resistance. However, ectopic expression of MTA1 in CNE1 cells induced CSCs phenotypes and CDDP insensitivity. Interestingly, ectopic overexpression of MTA1-induced CSCs properties and CDDP resistance were reversed in CNE1 cells after inhibition of PI3K/Akt by LY294002. In addition, MTA1 expression and Akt activity in CNE1/CDDP cells was much higher than that in CNE1 cells. These results suggested that MTA1 may play a critical role in promoting CDDP resistance in NPC cells by regulatingcancer stem cell properties via thePI3K/Akt signaling pathway. Our findings suggested that MTA1 may be a potential target for overcoming CDDP resistance in NPC therapy.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.1
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• pp.62-68
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• 2020

Cisplatin (CDDP) is a chemotherapy agent used for patients with ovarian cancers. CDDP activates multiple signaling pathways, which causes various cellular reactions according to the type of cancer cells. Therefore, it is difficult to clearly conclude its signaling pathways. The purpose of this study is to determine the role of the signal protein of Akt/ERK1/2 and MAPK by CDDP-induced apoptosis in ovarian cancer cells (SKOV3). As a result, the number of apoptosis increased according to the TUNEL assay, and flow cytometric analysis confirmed that the percentage of sub-G1 early apoptosis was 8.73% higher than the control. The PARP and caspase-3 activity that appeared in the process of apoptosis was increased and the Bcl-2 expression was decreased. It was verified that the Akt and ERK1/2 activity was decreased, and p38 and JNK activity increased in a time dependent fashion. In conclusion, these results demonstrate that cisplatin inhibits the proliferation of ovarian cancer cells by inhibiting Akt activity and induces apoptosis by modulating the MAPK signaling pathway. However, a decrease in the ERK1/2 activity by CDDP was the opposite result to the result shown from the HeLa cells. For this reason, further research on signaling pathways is necessary. These results are expected to be useful for ovarian cancer treatment strategies targeting the MAPK pathway.