• KSBB Journal
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• v.8 no.2
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• pp.110-114
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• 1993

Vinblastine, an anticancer agent was produced by chemical coupling of two different monomeric indole alkaloids, vinblastine and catharanthine in the presence of ferric ion. Vindoline was efficiently extracted from the leaves of vinca (Cafharanthus roseus) by using supercritical carbon dioxide, whereas catharanthine was chemically extracted from the in vitro cultured hairy roots. The extracted crude monomeric precursors were purified by a two-step preparative TLC. The coupling reaction was carried out in the 0.1M glycine buffer(pH 2.0, 5ml) containing 40mM FeC13 with purified vindoline(0.3mg) and catharanthine(0.3mg) at 4$^{\circ}C$. The production yields (weight %) of vinblastine and 3', 4'-anhy-drovinblastine in the products were 23.2 and 26.0, respectively. The produced vinblastine was confirmed by FAB-MS.

• Toxicological Research
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• v.6 no.1
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• pp.29-40
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• 1990

Cytotoxic effects of cytosine arabinoside and vinblastine on cultured fibroblasts were determined by colorimetric assays of neutral red (NR) and tetrazolium MTT, and by mutagenicity tests . Cytosine arabinoside and vinblastine were highly toxic by showing that concentrations of NR-50 and MTT-50 of two drugs were lower than 100 ${\mu}$M. At mid-point cytotoxicityvalue of two drugs, frequencies of micronuclei and SCEs were very high and chromosome showed structural abnormalities. The sizes of micronuclei formed by vinblastine were larger than those induced by cytosine arabinoside. These results suggest that cytosine arabinoside and vinblastine have highy mutagenic and severe cytotoxic effects on the cultured mouse fibroblasts.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.15 no.1
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• pp.35-48
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• 1993

The in vitro predictive tests in cancer chemotherapy of cancer cell lines to anticancer drugs were determined using novel dye exclusion assay [NDEA], [3H] thymidine incorporation, and clonogenic assay [CA>. Antitumor effect of Bleomycin, Cis-platin, Vinblastine, Methotrexate to HEp-2, B16 cell lines using rapid assays was compared with [CA> in this study. In dye exclusion assay of B l6 cell line, cancer cells were sensitive to Bleomycin at all concentrations, to Vinblastine at the level of peak plasma concentration [PPC], ${\times}1/10$ [PPC](P<0.05). And Bleomycin revealed relatively good cytotoxicity than that of CDDP and vinblastine at ${\times}10$[PPC], (P<0.05). HEp-2 cells were resistive to methotrexate at the level of ${\times}100$[PPC] (P<0.05) In [3H] thymidine incorporation assay, B 16 cells were sensitive to Bleomycin, CDDP, Vinblastine at the level of [PPC], ${\times}10$ [PPC](P<0.01). Dose-dependent drugs of bleomycin, CDDP were more sensitive than Vinblastine at high concentration (P<0.05). In clonogenic assay, HEp-2 cell line was sensitive to three drugs of all concentrations except ${\times}10$ [PPC] of CDDP. B 16 cell line was sensitive to all drugs(P<0,01). In comparison of chemosensitivity tests among three assays, the results were correlated(${\gamma}=0.99$, P<0.05).

• Korean Journal of Medicinal Crop Science
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• v.10 no.3
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• pp.212-216
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• 2002

Catharanthus roseus was extracted with methanol and its Vinblastine contents and antioxidant and antimicrobial activities in each methanol extracts were determined. Vinblastine contents of leaves were much higher than those in other plant parts. The highest DPPH(1,1-diphenyl-2 -picrylhydrazy) radical scavenging activities in plnat parts showed in leaves of Stardust Orchid and Cooler Rose and the value was $RC_{50}=17\;and\;18\;{\mu}g/ml$ respectively. Leaves of Cooler Rose and Coller Strawberry showed strong antimicrobial activities. Particularly, Cooler Rose showed strong antimicrobial activites except to Penicillium oxalicum.

• 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.

• Journal of Veterinary Clinics
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• v.24 no.4
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• pp.618-621
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• 2007

An 11-year-old, castrated male Yorkshire terrier dog was presented with multiple plaques on right inguinal region. Grade II mast cell tumor was diagnosed. The dog was treated with Vinblastine and prednisone(PDS) initially. Because of poor response of the dog, CCNU was added for more aggressive treatment. After 5 weeks treatment of with CCNU, vinblastine and PDS, the lesion was improved. Moderate leukopenia was shown after 4 cycles of chemotherapy. The chemotherapy was re-administered since the patient recovered from the leukopenia. Though the same protocol was applied, no improvement of the lesion was observed. Moreover, the general body condition of the dog became worse and was euthanized by the owner's request. Necropsy was not permitted. The survival time was 330 days after start of the chemotherapy.

• Biomedical Science Letters
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• v.2 no.1
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• pp.121-126
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• 1996

Specific monoclonal antibodies(mAbs) against bis-indole alkaloids related to vinblastine were established to develop a simple and specific immunoassay system for the quantitation of Vinca alkaloids. Vinca alkaloids were extracted from tissue cultured cells of periwinkle plant (Vinca rosea L.). Spleen cells from Balb/c mice immunized with vinblastine-bovine serum albumin(VBL-BSA) conjugate as immunogen were fused with myeloma cells(Sp2/0-Ag.14) in the presence of polyethylene glycol. In the preliminary experiments, 32 clones which highly reacted with VBL-BSA conjugate were selected by ELISA(Enzyme-linked immunosorbent assay).These clones were further analyzed by inhibition assay of ELISA. The results obtained with two typical monoclonal antibodies, KN-1 and KN-2, were described. KN-1 exhibited considerable reactivities with soluble dimeric bis-indole alkaloids, whereas no cross reacted with monomeric bis-indole alkaloids. However KN-2 showed cross reactivity with mono- and di-meric bis-indole alkaloids. Furthermore, KN-1 was applied to the immunoassay system for determining the VBL amounts of in vitro cultured cell extracts. This assay system could detect dimeric vinca alkaloid as low as 0.05 nM.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.105-105
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• 2002

염색체의 구조적 이상으로 인한 습관성 유산과 기형아의 출산을 예방하기 위해 착상전 배아에서 할구를 분석하여 정상적인 핵형을 가진 배아만을 이식하는 착상전 유전자 진단 (preimplantation genetic diagnosis, PGD)의 성공적인 임상 적용이 보고되고 있으며, 그 적용 범위가 확대되고 있다. 그러나 일반적인 간기의 핵상을 이용한 PGD에서는 형광직접보합법 probe의 제약으로 보인자와 정상적인 핵형을 구분할 수 없는 단점이 있다. 따라서 본 연구에서는 보다 정확한 PGD를 위해 생쥐 배아를 이용하여 분리한 할구에서 중기 염색체상을 획득하기 위해 미세소관 (microtubule) 형성 저해제를 처리하였으며, 이를 통해 확립된 방법을 인간의 PGD에 적용하고자 하였다. 과배란이 유도된 ICR 생쥐에서 4- 또는 8-세포기 배아를 수획하여 colcemid, nocodazole, vinblastine을 각각 0.1, 0.5, 1.0, 5.0$\mu$M을 처리하고, hoechst 33342로 염색하여 핵상을 관찰하여 최적의 농도를 결정하였다. 또한 각 미세소관 형성 저해제를 혼합 처리하여 가장 높은 중기 염색체상을 획득할 수 있는 혼합 처리를 결정하였다. 이렇게 결정된 혼합 처리 방법을 인간의 체외 수정 및 배아 이식술에서 획득된 3PN 배아에 처리하여 중기 염색체를 획득하였다. Colcemid, nocodazole, vinblastine 모두 1 $\mu$M이 최적 농도임을 확인할 수 있었다 (각각 96.3%, 92.0%, 98,4%). 미세소관 형성저해제를 혼합 처리하였을 경우 nocodazole과 vinblastine (각각 1$\mu$M)을 혼합 처리했을 때 중기 염색체 획득률(97.3%)이 가장 높았다. 인간의 3PN 배아에 1$\mu$M의 nocodazole과 vinblastine을 혼합 처리한 후, 113개의 할구를 분석하여 44개(38.9%)의 할구에서 중기 염색체를 확인할 수 있었다. 본 실험 결과를 통해 중기 염색체를 획득하기 위하여 미세소관 형성 저해제를 처리하는 방법은 생쥐의 배아에서는 효과적이지만, 인간의 배아에서는 그 효율이 다소 낮음을 알 수 있었다. 그러나 이 방법을 개선하여 인간의 할구에서 중기 염색체의 획득률을 높이고, 이를 염색체의 구조적 이상에 대한 착상전 유전자 진단에 적용한다면, 보인자와 정상의 핵상을 구분하여 정상의 핵상만을 갖는 배아의 이식을 통하여 더욱 정확한 착상전 유전자 진단을 시행할 수 있으리라 사료된다.

• Korean Journal of Pharmacognosy
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• v.17 no.3
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• pp.248-254
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• 1986

Effects of vinblastine(VLB) and vincristine(VCR) on cell-mediated immunity(CMI) were studied with the microcytotoxicity test(MCT) after normal or pre-sensitized Balb/c mice had been treated in vivo with a combination of two different doses of VLB or VCR(single dose of 20% and 60% $LD_{50}$, i.p.) at different times (from day -6 to day +4) plus allo-transplantation antigen(allo-TA, cells from C3H mice at day 0). The results were that $LD_{50}$ of VLB for female Balb/c mouse was 7.3mg/kg body weight (i.p.) and $LD_{50}$ of VCR was 4.3mg/kg body weight and that VLB and VCR acted as immunosuppressive agents on the primary CMI when administered after allo-TA(antigen-drug-phase), but showed no effect when administered prior to allo-TA(drug-antigen-phase). Change of doses of VLB and VCR(20% $LD_{50}$, 60% $LD_{50}$) caused quantitative or qualitative variations in the immunomodulating effects of these two drugs. Neither VLB nor VCR had any immunomodulating effect on the secondary CMI. Lastly, the results support that the four parameters (type of drug, sensitization status, time of drug treatment in relation to antigen injection, and drug dosis) are significant for the effects of the VLB and VCR on the CMI, and that VLB and VCR may inhibit the proliferation of antigen-stimulated T effector lymphocytes but not memory-cytotoxic T lymphocytes.

• Journal of Yeungnam Medical Science
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• v.9 no.1
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• pp.75-89
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• 1992

The development of multi drug-resistant tumor cell population is a major problem in the chemotherapy of human cancer. These cells are often cross resistant to unrelated drugs and the precise mechanisms of multidrug resistant phenotype of tumor cells has not been fully elucidated. Cisplatin resistant tumor cell(SNU-1/$Cis_5$) was induced from human stomach cancer cell line(SNU-1) in vitro. Growth profiles of survival cells were observed during 5 days by thiazolyl blue (MTT) assay. To investigate the cross resistance of various anticancer drugs in SNU-1 and SNU-1/$Cis_5$, We compared the value of $IC_{50}$ - drug concentration at 50% survival of control and gained relative resistances (RR). The RR for SNU-1/$Cis_5$ were as follows; vinblastine, > 43.0 ; epirubicin, 22.9 ; dactinomycin, 16.0 ; etoposide, 15.0 ; vincristine, 9.2 ; adriamycin, 5.7 ; aclarubicin, 5.3. But 5-fluorouracil, methotrexate, daunorubicin have not cross resistance with cisplatin. Resistant inhibition values of $10{\mu}M$ verapamil for SNU-1/$Cis_5$ were as follows; vincristine, 13.1 ; epirubicin, 10.0 ; etoposide, 6.3 ; vinblastine, 4.4 ; dactinomycin, 3.6 ; daunorubicin, 2.4. Membrane proteins of 51,400 and 81,300 daltons were identified by radioiodination with SDS-PAGE, which might represented the drug resistance.