• Journal of Microbiology and Biotechnology
• /
• 제8권5호
• /
• pp.455-460
• /
• 1998

In the course of screening for new antitumor substances, a novel cytotoxic agent inducing apoptotic cell death was isolated from the culture broth of marine bacterial strain SCRC A-20. Strain SCRC A-20 was separated from a mollusk and was chemotaxonomically identified as a Streptomyces sp. The cytotoxic substance was purified by organic solvent extraction followed by silica gel column chromatography and preparative TLC. HRFAB-MS determined its molecular formula to be $C_{30}H_{40}N_2O_5$ (MW 508). The 1D and 2D NMR spectral data demonstrated that the substance has a novel lactam structure of a 20-membered macrocycle coupled with a unique acyl tetramine and bicyclo［3.3.0］ octane, which includes three methyl groups, six olefinic protons, five carbonyl groups, a conjugated diene and a dienone. The substance, named aburatubolactam C, appeared to be cytotoxic for various continuously proliferating tumor cells of human and murine origins. The $IC_{50}$ values determined by MIT assay were in the range of 0.3 to $5.8\mug/ml$. When Jurkat T cells were treated with $3\mug/ml$. of aburatubolactam C, the apoptotic DNA fragmentation was detectable within 3 h, indicating that the cytotoxic effect of aburatubolactam C on tumor cells is attributable to the induced apoptosis.

• 혜화의학회지
• /
• 제4권2호
• /
• pp.273-297
• /
• 1996

Hexane fraction of Oldenlandiae diffusae Herba(ODH) which was being used for the treatment of caner in oriental medicine showed the best cytotoxicity against L1210 and A549 in the solvent fractions. Antitumor substance isolated from hexane fraction of ODH was identified as ursolic acid(UA) by photometric analysis. IC50 of UA against cancer cells as SNU-1, HCT15, XF498, SK-MEL2 and A549 was $13{\mu}g/m{\ell}$, $15{\mu}g/m{\ell}$, $12{\mu}g/m{\ell}$, $9{\mu}g/m{\ell}$ and $11{\mu}g/m{\ell}$ respectively. It significantly inhibited the metastasis to lungs and kidneys from pulmonary colonization assay and study on histological changes of organs and showed the enhancing effect on B cell dosage-dependently by FACS analysis. T/C % of UA against S-180 cells was 171 % and its cytotoxicity against SNU-1 iant was confirmed from the morphological changes by elctronic microscopes such as SEM and TEM that it induced undulated membrane 4 hr after UA treatment, and the breakdown of cell membrane and nucleus 24 hr after UA treatment.

• 한국미생물·생명공학회지
• /
• 제30권1호
• /
• pp.51-56
• /
• 2002

국내 토양에서 분리한 식물성 병원균인 Alternaria brassicicola SW-3리 항암활성 물질 생산능을 조사하고, 활성물질을 분리 정제하여 구조를 확인하였다. A. brassicicola SW-3는potato dextrose broth를 이용하여 15$^{\circ}C$에서 2주간 진탕 배양한 다음, MTT assay를 실시하여 항암활성을 확인하였으며, 배양여액 중의 항암물질은 ethyl acetate로 추출하고, silica gel column chromatography로 정제하여 무색의 oily product를 얻었다(수율 22mg/m1). 분리된 물질은 물이나 hexane에는 녹지 않고, chloroform, ethyl acetate, ethanol 등에는 잘 녹는 특징을 보였으며, , $IR^{1}$H-NMR, $^{13}$C-NMR 등을 통해 구조를 분석한 결과, 최근에 일본에서 분리되어 항암효과가 있는 것으로 알려진 depudecin과 동일한 물질로 추정되었다. 본 실험에서 분리된 depudecin은 인체간암세포와 mouse 피부암세포에 대한 세포독성을 나타내었으며, 각각의$ IC_50$ 는 $57\mu$g/ml, $69\mu$g/ml로 나타났다. Alternaria brassicicola SW-3에 의해 생산된 물질이 기지의 물질이지만, depudecin은 아직 작용 기작이나 적용범위 등이 밝혀지지 않은 초기 연구 단계에 있는 물질로서, 새로운 항암제로서의 가능성이 매우 높아 이의 유도체를 합성하거나, 다른 항암제와의 혼용에 의해 부작용이 적은 강력한 항암제를 개발하기 위한 선도물질로 활용될 수 있을 것이다.

• 고려인삼학회:학술대회논문집
• /
• 고려인삼학회 1988년도 학술대회지
• /
• pp.33-35
• /
• 1988

우리는 경험적으로 인삼이 훌륭한 치료효과로서 항종양효과가 있다는 것을 알고 있다. 인삼으로부터 종양발육 억제효과가 있는 물질을 분리하는 과정에서 우리는 새로운 타입의 항종양 물질을 발견하였다. 이물질은 Panax ginseng C.A. Mayer의 분말로부터 분리하였는데 이 분말은 일본에서 홍삼분말이라는 이름으로 의약품으로서 여러가지 질병치료에 사용되고 있다. IR, $^{1}H,\;^{13}C-NMR$ 및 MS에 의한 분석결과로 이 물질은 panaxytriol로 동정 되었다. 고려홍삼에서 분리된 panaxytriol은 in vitro 시험에서 몇가지의 인체암세포와 악성백혈병 세포의 성장을 억제하였다. 비록 panaxytriol에 의한 세포성장억제에 대한 상세한 작용기전은 알려져있지 않으나 panaxytriol의 효과는 처리시간보다는 농도 의존성이 있는 것으로 밝혀졌다.

• 약학회지
• /
• 제44권6호
• /
• pp.601-606
• /
• 2000

Recently, studies on missile antitumor drugs, which selectively act on tumor cell and display drug effects, have been performed. These missile antitumor drugs which can increase drug effects and decrease side effects, are ideal medication method. Lectin has been reported as tumor cell specific binding protein and tannin as antitumor substance. In this study, we studied inhibition of melanoma metastasis by lectin-conjugated ellagitannin and used praecoxin A as ellagitannin source. Mouse melanoma cell, B16-F10, was injected into the sole of forefoot of C57BL/6 mouse, and after administration with drug, the number of pulmonary tumor colony was counted. The administration of praecoxin A, lectin-praecoxin A mixiture, and lectin-conjugated praecoxin A was started after amputation of established tumor foci at right forefoot of mice and continued for 3 weeks with i.p. injection of one of those drugs A every 24 hours. Lectin-praecoxin A mixture, and lectin-conjugated praecoxin A significantly reduced the number of spontaneous pulmonary metastasis. Exposure to 5 mg/kg of lectin-praecoxin A mixiture and lectin-conjugated praecoxin A produced a statistically significant 38.3%, 41.8% reduction in the number of remaining pulmonary metastasis. These results suggest that metastasis inhibition by lectin-praecoxin A mixiture and lectin-conjugated praecoxin A are better than that of praecoxin A.

• 한국축산식품학회지
• /
• 제24권3호
• /
• pp.293-297
• /
• 2004

본 연구에서는 유황오리로부터 항종양 효과를 나타내는 물질을 용매 추출법과 각종 크로마토그래피를 사용하여 분리 및 정제하였다. 유황오리로부터 정제한 활성 물질의 각종 종양세포에 대한 항암 효과를 측정한 결과 MTT assay는 100 $\mu\textrm{g}$/mL의 농도에서 HEp-2는 56%, KB는 58%의 세포 증식 억제 효과가 나타났다. 정상 세포주인 MDBK는 28%의 세포증식억제 효과가 나타나 정상 세포에 대한 세포 독성은 나타나지 않았다. Clonogenic assay는 200 $\mu\textrm{g}$/mL의 농도에서 HEp-2는 26%, KB는 28%의 생존율을 나타내었다. 따라서 유황오리로부터 정제한 활성 물질은 후두암 세포주인 HEp-2와 구강암 세포주인 KB에서만 특이적으로 세포 증식 억제 효과를 나타내었다.

• 한국미생물·생명공학회지
• /
• 제22권3호
• /
• pp.322-328
• /
• 1994

Antitumor and immunoadjuvant activities of Bifidobacterium adolesentis ATCC-15703 were investigated against the ascites and solid forms of tumor induced by Sarcoma 180(S-180) in ICR mice. When 100 $\mu$g of the bacterium was intraperitonealy administered in the mice, the survival rate(T/C %) of the mice was 132% for 50 days after the inoculation of S-180, however the increment of their body weights was suppressed. When the 100 $\mu$g was subcutaneously adminis- tratered at the right grion, the suppresion rate of the tumor growth on the 21st day after inoculation of S-180 were 62.3%. Complete supression of the tumor growth was observed from 2 out of 8 test mice. The bacterium itself appeared to have noncytotoxic substance against the S-180 in vitro. The bacteria] administration markedly enhanced the activity of peritoneal macrophages. The num- ber of peritoneal macrophages at one day after the administration of the 100 $\mu$g increased about 8 times as much as that of the control, and the highest activity of acid phosphatase appeared at 2 days.

• 한국미생물·생명공학회지
• /
• 제26권6호
• /
• pp.471-475
• /
• 1998

신생아 분변으로부터 장내세균 127균주를 분리하였다. 각각의 균주들의 배양균체를 검정종양세포들에 대해 항종양활성을 측정한 결과, 항종양활성을 나타내는 분리균주는 27균주였고, 그 중 비교적 강한 항종양활성을 보이는 균주는 5균주였으며, 5균주중 위암세포주, SNU-1에 선택적으로 강한 항종양활성을 나타내는 2B4-1 균주를 최종분리하였다. API 20 S system kit를 이용하여 분리 균주 2B4-1을 동정한 결과, Enterococcus faecalis와 99.9%의 % ID value를 나타내었다. 동정된 분리균주 2B4-1과 type strain, Enterococcus faecalis NCTC 775와의 생리생화학적 특성들을 비교해 본 결과, 온도별대 성장률, 내염성, 내산성, arabinose등의 당 이용성 및 통성혐기 상태에서의 생육 등에서는 일치된 결과를 나타내었으나 hippurate hydrolysis test의 음성반응 및 $\beta$-hemolysis test의 음성반응을 나타낸 것으로 보아 Enterococcus faecalis NCTC 775와 2가지의 다른 특성을 나타내었다. 따라서 분리균주 2B4-1은 Enterococus faecalis NCTC 775와는 약간의 특성이 다른 변종으로 확인되어 Enterococcus faecalis 2B4-1으로 동정하였다.

• 한국자원식물학회지
• /
• 제6권1호
• /
• pp.13-23
• /
• 1993

To data, many types of compounds having antineoplastic activity have been isolated from higher plants, that is, alkalodids, terpenes, lignans, steroids and so on. Some of ther were isolated from Indonesian plants, Curcuma xanthorrhiza and Eurycoma longifolia. Bisaborane type compounds were compounds were isolated as antimeoplastic compounds againest Sarcoma 180A from C. xanthorrhiza, and quassinoids and euryrene type triterpenes from triterpenes from El longifolia. Casearines, a kind of diterpene, had been isolated as cytotxic components from Casearia sylvestris distributed in South America. RA series Cyclic hexapeptides isolated from Rubia akane and R. cordifolia also have strong antineoplastic activity against various types of tumors. Till now, 16 kinds of RA series compounds were isolated and named as RA-I~XVI. Moreover, monoglucoside of RA-V newly isolated from same plant. Many kinds of derivatives including natural RA compounds were tested for QSAR, and one of them, RA-VII was screened up as a most suitable substance as an antitumor agent. RA-VII(=RA 700) has strong cytotoxic activity against KB cells, P388 lymphocytic leukemia and MM2 mammary carcinoma cells. In some solution, three conformers of RA-VII were observed by NMR. It was discussed the relationship between conformation and activity. Total synthesis was already completed, but there is left room for improvement. Phase I clinical trials for RA-VII has been finished, then Phase II trials will be started before long.

• Biomolecules & Therapeutics
• /
• 제2권1호
• /
• pp.82-93
• /
• 1994

DA-125, a new anthracycline antitumor antibiotic, was at dose levels of 0, 0.1, 0.3 and 1.0 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of Fl fetuses, as well as growth, behaviour and mating performance of Fl offspring were examined. 1. At 1 mg/kg, one out of the 10 dams showed difficult delivery. A decrease in food consumption, a loss in body weight and a decrease of spleen weight were found in this dose level group. At 0.3 mg/kg, difficult deliverys were observed in two out of the 10 dams. 2. At 1 mg/kg, an increased resorption rate and a decreased fetal weight were found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. 3. At 1 mg/kg, body weight reduction, small eyeball, hydrocephalus and atrophy of sexual organs were observed in Fl offspring. One male pup receiving 0.3 mg/kg died on day 2 of lactation. The results show that the no-effect dose levels (NOELs) for dams and Fl offspring are 0.1 mg/kg/day and NOEL for Fl fetuses is 0.3 mg/kg/day.