• Title, Summary, Keyword: chemotherapeutic drugs

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CSE1L/CAS, a microtubule-associated protein, inhibits taxol (paclitaxel)-induced apoptosis but enhances cancer cell apoptosis induced by various chemotherapeutic drugs

  • Liao, Ching-Fong;Luo, Shue-Fen;Shen, Tzu-Yun;Lin, Chin-Huang;Chien, Jung-Tsun;Du, Shin-Yi;Jiang, Ming-Chung
    • BMB Reports
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    • v.41 no.3
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    • pp.210-216
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    • 2008
  • CSE1L/CAS, a microtubule-associated, cellular apoptosis susceptibility protein, is highly expressed in various cancers. Microtubules are the target of paclitaxel-induced apoptosis. We studied the effects of increased or reduced CAS expression on cancer cell apoptosis induced by chemotherapeutic drugs including paclitaxel. Our results showed that CAS overexpression enhanced apoptosis induced by doxorubicin, 5-fluorour-acil, cisplatin, and tamoxifen, but inhibited paclitaxel-induced apoptosis of cancer cells. Reductions in CAS produced opposite results. CAS overexpression enhanced p53 accumulation induced by doxorubicin, 5-fluorouracil, cisplatin, tamoxifen, and etoposide. CAS was associated with $\alpha$-tubulin and $\beta$-tubulin and enhanced the association between $\alpha$-tubulin and $\beta$-tubulin. Paclitaxel can induce G2/M phase cell cycle arrest and microtubule aster formation during apoptosis induction, but CAS overexpression reduced paclitaxel-induced G2/M phase cell cycle arrest and microtubule aster formation. Our results indicate that CAS may play an important role in regulating the cytotoxicities of chemotherapeutic drugs used in cancer chemotherapy against cancer cells.

Effects of Hydroxychloroquine Co-administered with Chemotherapeutic Agents on Malignant Glioma Cell Lines : in vitro Study

  • Park, Yong-Sook;Choi, Jae-Young;Chang, Jong-Hee;Park, Yong-Gou;Chang, Jin-Woo
    • Journal of Korean Neurosurgical Society
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    • v.38 no.1
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    • pp.47-53
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    • 2005
  • Objective : Anti-malaria drugs may modulate tumor resistance to chemotherapeutic agents, but it has not been proven effective in the treatment of malignant gliomas. The aim of this study was to determine whether adequate pre-clinical data on co-administration of chemotherapeutic agents with anti-malaria drugs on malignant cell lines could be obtained that would warrant its further potential consideration for use in a clinical trial for malignant gliomas. Methods : Two malignant glioma cell lines [U87MG, T98G] were treated with chemotherapeutic agents alone or with anti-malaria drugs. Cells were incubated with drugs for 4 days. Following the 4-day incubation, drug sensitivity assays were performed using 3-[4,5-dimethyl-2-thiazol-2-yl] 2,5-diphenyltetrazolium bromide [MTT] assay following optimization of experimental conditions for each cell lines and cell viability was calculated. Results : In all of four chemotherapeutic agents[doxorubicin. vincrisitne, nimustine, and cisplatin], the cell viability was found to be markedly decreased when hydroxychloroquine was co-administered on both U87MG and T98G cell lines. The two way analysis of variance[ANOVA] yielded a statistically significant two-sided p-value of 0.0033[doxorubicin], 0.0005[vincrisitne], 0.0007[nimustine], and 0.0003[cisplatin] on U87MG cell lines and 0.0006[doxorubicin], 0.0421[vincrisitne], 0.0317[nimustine], and 0.0001[cisplatin] on T98G cell lines, respectively. However, treatment with chloroquine and primaquine did not induce a decrease in cell viability on both U87MG and T98G cell lines. Conclusion : Our data support further consideration of the use of hydroxychloroquine prior to systemic chemotherapy to maximize its tumoricidal effect for patients with malignant gliomas.

A Novel Monoclonal Antibody Induces Cancer Cell Apoptosis and Enhances the Activity of Chemotherapeutic Drugs

  • Xu, Heng;Tian, Yan-Na;Dun, Bo-Ying;Liu, Hai-Tao;Dong, Guang-Kuo;Wang, Jin-Hua;Lu, Shang-Su;Chen, Bo;She, Jin-Xiong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4423-4428
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    • 2014
  • A novel monoclonal antibody (mAb), known as AC10364, was identified from an antibody library generated by immunization of mice with human carcinoma cells. The mAb recognized proteins in lysates from multiple carcinoma cell lines. Cell cytotoxicity assays showed that AC10364 significantly inhibited cell growth and induced apoptosis in multiple carcinoma cell lines, including Bel/fu, KATO-III and A2780. Compared with mAb AC10364 or chemotherapeutic drugs alone, the combination of mAb AC10364 with chemotherapeutic drugs demonstrated enhanced growth inhibitory effects on carcinoma cells. These results suggest that mAb AC10364 is a promising candidate for cancer therapy.

Effect of Deer Blood on Reduction of the Side Effects of Chemotherapeutic Drugs (녹혈의 화학요법 항암제 부작용 억제 효능)

  • Kim, Han-Seob;Hong, Soon-Bok;Sung, Hyun-Jea;Moon, Geun-Ah;Yoon, Yoo-Sik
    • Korean Journal of Pharmacognosy
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    • v.34 no.2
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    • pp.145-149
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    • 2003
  • Many chemotherapeutic drugs were developed and contributed to the increase of cure rate of cancer, however severe side effect of these drugs is a major cause of poor quality of life of cancer patients. Effect of deer blood on cancer therapy was investigated in mouse tumor model. Deer blood itself was shown to have mild antitumor activity. However it has significant effect on the reduction of the side effects of chemotherapy. Deer blood recovered the reduction of WBC and platelet (myelotoxicity) during fluorouracil chemotherapy. Deer blood also recovered the increase of serum blood urea nitrogen (BUN; indicator of renal toxicity) and increase of serum amylase activity (AMY; indicator of pancreatic toxicity) almost to the control level during cisplatin chemotherapy. Fluorouracil and cisplatin are major chemotherapeutic drugs which are currently used in clinical cancer therapy, and the results strongly suggest that deer blood can be used for reducing the side effects and improving the quality of life during chemotherapy of cancer patients.

Alternative drug therapies are superior to epidermal growth factor receptor -targeted chemotherapeutic drug responses in non-small cell lung cancer

  • Sikdar, Sourav;Khuda-Bukhsh, Anisur Rahman
    • CELLMED
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    • v.3 no.2
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    • pp.10.1-10.8
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    • 2013
  • Cancer is one of the major dreaded diseases causing high mortality. Lung cancer is second in position of all cancer related deaths and mainly divided into two morphologic sub-types: small-cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is an aggressive neoplasm which hardly responds to any conventional chemotherapy. Epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinase that is mainly over-expressed in NSCLC. EGFR is mainly involved in the pathogenesis and progression of different carcinoma. In vivo and in vitro studies suggest that EGFR and EGF like peptides are often over-expressed in human NSCLC and these proteins are able to induce cell transformation. The conventional therapies mostly inhibit the EGFR activity and expression level in human NSCLC with the use of some EGFR-inhibitors like HKI-272, EKB569, CL-387785 etc. and some synthetic chemotherapeutic drugs like erlotinib, gefitinib, plumbagin, docetaxel, cisplatin etc., alone or in combination of two or more drugs. These therapies selectively act by competitive inhibition of the binding of adenosine triphosphate to the tyrosine kinase domain of the EGFR, resulting in inhibition of the EGFR signaling pathway. But these chemotherapeutic drugs have some cytotoxic activities to the normal cells and have some adverse side-effects. Recent studies on some traditional alternative therapies including some herbal and plant extracts, active ingredients like curcumin, different homeopathic drugs, etc. can target EGFR-signalling in NSCLC with less toxic side-effects are being currently developed.

Studies on Metal Chelation of Chemotherapeutic Agents.(V) Structures of Cu-Sulfa Drug Complexes (화학료법제의 금속 chelate 화합물에 관한 연구 (V) Sulfa 제-Cu 착화합물의 구조)

  • 이왕규
    • YAKHAK HOEJI
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    • v.13 no.2_3
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    • pp.97-100
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    • 1969
  • As a part of an effort to find a relationship between metal chelation and its chemotherapeutic activity change for sulfa drugs, Sulfadimethoxine, Sulfamerazine Sulfamethoxy-pyridazine-Cu(II) complex compounds were studied through IR spectra.

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Sensitivity of Bordetella bronchise ptica Isolated from Pigs Affected by Infectious Atrophic Rhinitis to Chemotherapeutic Agents (전염성위축성비염돈(傳染性萎縮性鼻炎豚)으로부터 분리(分離)한 Bordetella bronchiseptica의 화학요법제(化學療法劑)에 대(對)한 감수성시험(感受性試驗))

  • Kang, Byong Kyu
    • Korean Journal of Veterinary Research
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    • v.20 no.2
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    • pp.159-165
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    • 1980
  • A total of 98 strains of Bordetella bronckiseptica isolated from pigs affected the infectious atrophic rhinitis(AR) during 1978 were surveyed for drug sensitivity to 26 chemotherapeutic agents, and minimum inhibitory concentration(MIC), incidence rate of resistant strain and resistant patern from the strains which were obtained from the different pig farm in Jeonnam province were examined. The results obtained are summarized as follows. 1. Most of the strains tested were resistant to Ampicillin (AB, PC), spiramycin(SPO, sulfa drugs (SD) (MIC:$400.0{{\mu}g/ml}$) and streptomycin(SM) (MIC:$200.0{{\mu}g/ml}$). Of the 75.0% of strains were also resistant to penicillin(PC) (MIC:$200.0{{\mu}g/ml}$) and of the 14.3 of strains were inhibited to grow to tetracycline(TC), chlortetracycline(CTC), oxytetracyc-line(OTC), erythromycin(EM), tylosin(TS), leucomycin (LM) and chloramphenicol (CP) (MIC:$6.25{{\mu}g/ml}$). On the other hand, most of the strains tested were inhibited to grow to kanamycin(KM), gentamycin(GM) neomycin(NM) (MIC:$25.0{{\mu}g/ml}$) and to colistin(CL) (MIC:$12.5{{\mu}g/ml}$). 2. Incidence rate of resistant strains to main chemotherapeutic agents was 100.0% of sulfa drugs, 96.4% of streptomycin, 85.7% of penicillin, tetracycline, chloramphenicol and erythromycin, 46.4% of gentamycin, 17.9% of colistin and 0.0% of kanamycin and nalidixic acid.

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Synergistic Effect of Cisplatin and Berberine on Inhibition of Cell Growth and Induction of Apoptosis involving Oxidative Stress in HeLa Cells (자궁경부암 세포주에서 활성산소종의 영향애 의한 Apoptosis를 통하여 세포성장을 억제하는 Cisplatin과 Berberine의 상승효과)

  • Cho, Hae-Joong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.4
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    • pp.992-997
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    • 2007
  • Cisplatin is a chemotherapeutic drug which is widely used for cancer therapy including cervical cancer. The purpose of this study is to elucidate synergistic effect of Cisplatin and Berberine on the apoptosis of HeLa cells and to determine whether oxidants are formed as part of apoptotic process. Apoptotic death of HeLa cells by cisplatin and berberine was confirmed by chromatin condensation of HeLa cells and flow cytometric analysis of intracellular ROS(reactive oxygen species) production. In MTT assay, Cell viability was decreased and enhanced ROS generation in combination of cisplatin and berberine significantly, as compared with cisplatin only. Synergistic effect of Cisplatin and Berberine on the inhibition of cell growth by apoptosis was clearly observed and ROS may play an important role in apoptosis. This effect suggest the possibility lowering the concentration of chemotherapeutic drugs, which alleviate the side effect of drugs.

Aprepitant in the Prevention of Vomiting Induced by Moderately and Highly Emetogenic Chemotherapy

  • Wang, Shi-Yong;Yang, Zhen-Jun;Zhang, Zhe;Zhang, Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10045-10051
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    • 2015
  • Chemotherapy is a major therapeutic approach for malignant neoplasms; however, due to the most common adverse events of nausea and vomiting, scheduled chemotherapeutic programs may be impeded or even interrupted, which severely impairs the efficacy. Aprepitants, 5-HT3 antagonists and dexamethasone are primary drugs used to prevent chemotherapy-induced nausea and vomiting (CINV). These drugs have excellent efficacy for control of acute vomiting but are relatively ineffective for delayed vomiting. Aprepitant may remedy this deficiency. Substance P was discovered in the 1930s and its association with vomiting was confirmed in the 1950s. This was followed by a period of non-peptide neurokinin-1 (NK-1) receptor antagonist synthesis and investigation in preclinical studies and clinical trials (phases I, II and III). The FDA granted permission for the clinical chemotherapeutic use of aprepitant in 2003. At present, the combined use of aprepitant, 5-HT3 antagonists and dexamethasone satisfactorily controls vomiting but not nausea. Therefore, new therapeutic approaches and drugs are still needed.

Cytotoxic and Apoptotic-inducing Effects of Purple Rice Extracts and Chemotherapeutic Drugs on Human Cancer Cell Lines

  • Banjerdpongchai, Ratana;Wudtiwai, Benjawan;Sringarm, Korawan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6541-6548
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    • 2013
  • Pigmented rice is mainly black, red, and dark purple, and contains a variety of flavones, tannin, polyphenols, sterols, tocopherols, ${\gamma}$-oryzanols, amino acids, and essential oils. The present study evaluated the cytotoxic effects of purple rice extracts (PREs) combined with chemotherapeutic drugs on human cancer cells and mechanisms of cell death. Methanolic (MeOH) and dichloromethane (DCM) extracts of three cultivars of purple rice in Thailand: Doisaket (DSK), Nan and Payao (PYO), were tested and compared with white rice (KK6). Cytotoxicity was determined by 3-(4, 5-dimethyl)-2, 5-diphenyltetrazolium bromide (MTT) assay in human hepatocellular carcinoma HepG2, prostate cancer LNCaP and murine normal fibroblast NIH3T3 cells. MeOH-PYO-PRE was the most cytotoxic and inhibited HepG2 cell growth more than that of LNCaP cells but was not toxic to NIH3T3 cells. When PREs were combined with paclitaxel or vinblastine, they showed additive cytotoxic effects on HepG2 and LNCaP cells, except for MeOH-PYO-PRE which showed synergistic effects on HepG2 cells when combined with vinblastine. MeOH-PYO-PRE plus vinblastine induced HepG2 cell apoptosis with loss of mitochondrial transmembrane potential (MTP) but no ROS production. MeOH-PYO-PRE-treated HepG2 cells underwent apoptosis via caspase-9 and-3 activation. The level of ${\gamma}$-oryzanol was highest in DCM-PYO-PRE (44.17 mg/g) whereas anthocyanin content was high in MeOH-PYO-PRE (5.80 mg/g). In conclusion, methanolic Payao purple rice extract was mostly toxic to human HepG2 cells and synergistically enhanced the cytotoxicity of vinblastine. Human HepG2 cell apoptosis induced by MeOH-PYO-PRE and vinblastine was mediated through a mitochondrial pathway.