• Journal of Ginseng Research
• /
• 제33권4호
• /
• pp.367-377
• /
• 2009

구강악취 원인 물질인 $H_2S$를 발생시키는 NaHS로 RAW 264.7 세포를 자극시킨 결과, VSCs 생성에 관련된 CSE 유전자 발현증가와 함께 IL-6, COX-2, iNOS와 같은 염증매개 cytokine이 증가하며, 아울러 본 대식세포나 백혈구 활성에 관련된 세포내 골격단백질인 ERM의 발현증가가 유도되었다. 이러한 사실은 이전의 연구결과인 VSCs의 생성이 위점막 염증 및 손상과 연관되어 있다는 이전의 연구를 증빙해주는 사실인데, 더욱 흥미로운 사실은 고려 홍삼의 전처치를 통하여 CSE의 억제는 물론 염증 연관 cytokine 및 ERM의 발현억제를 유도할 수 있으며, 이는 세포내 신호전달계인 p38 및 ERK의 억제, 주로는 ERK 비활성화를 통하여 작동됨을 규명하였다. 고려홍삼이 구강악취 환자에게서 증상 완화내지는 소멸을 위하여 매우 유용하다는 이전의 연구결과에 본 연구결과가 추가됨으로 고려홍삼에 의한 VSC 생성억제 기전이 관련된 유전자의 약화는 물론 cytokine 억제 및 백혈구 활성에 관련된 인자억제를 통한 항염증 작용에 근거한다는 기전을 추가할 수 있었다.

• Biomolecules & Therapeutics
• /
• 제5권3호
• /
• pp.278-283
• /
• 1997

DW-166HC ($^{166}$ Holmium ($^{166}$ Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumoriginec spectrum, especially against human fepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous and intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I ($^{165}$ Ho-Chitosan complex cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC ($^{166}$ Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr and 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative control group but there was significant difference this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.

• 생명과학회지
• /
• 제25권9호
• /
• pp.984-992
• /
• 2015

혈근초(Sanguinaria canadensis)에서 처음 분리된 sanguinarine은 항산화, 항암 및 면역 증강 등의 효능이 있는 것으로 알려진 alkaloid 계열 물질 중의 하나이다. 본 연구에서는 인체간암 HepG2 세포를 대상으로 sanguinarine의 apoptosis 유도 효능 및 관련 기전 해석을 시도하였다. 본 연구의 결과에 의하면 sanguinarine은 HepG2 간암세포의 증식을 처리 농도 의존적으로 억제하였으며, 이는 apoptosis 유도와 연관성이 있었다. Sanguinarine에 의한 apoptosis 유도에는 Fas 및 Bax의 발현 증가, 미토콘드리아에서 세포질로의 cytochrome c 유리 및 MMPl (Δψm)의 소실을 동반하였다. Sanguinarine은 intrinsic 및 extrinsic apoptosis pathway의 활성에 관여하는 initiator caspase인 caspase-9와 -8의 활성과 effector caspase인 caspase-3의 활성 및 PARP 단백질의 단편화를 유발하였다. Sanguinarine은 또한 ROS의 생성을 촉진시켰으며, N-acetylcysteine 처리에 의한 ROS의 생성을 차단하였을 경우, sanguinarine에 의한 apoptosis 효능이 완벽하게 차단되었다. 아울러 sanguinarine은 Akt의 인산화를 억제한 반면, MAPKs의 인산화를 촉진시켰으며, 특히 PI3K와 ERK의 선택적 억제제는 sanguinarine에 의한 HepG2 간암세포의 증식을 더욱 억제시켰다. 따라서 sanguinarine에 의한 HepG2 간암세포의 apoptosis 유발에는 ROS 생성 의존적인 intrinsic 및 extrinsic signaling pathway가 동시에 활성화되며, PI3K/Akt 및 ERK 신호계가 관여함을 알 수 있었다.

• 대한정형도수물리치료학회지
• /
• 제11권2호
• /
• pp.62-70
• /
• 2005

The determination of peripheral nerve conduction velocity is an important part to electrodiagnosis. Its value as neurophysiologic investigative procedure has been known for many years but normal value of median and ulnar motor nerve was poorly reported in Korea. To evaluate of median and ulnar motor nerve terminal latency, amplitude of CMAP(compound muscle action potential), conduction velocity and F-wave latency for obtain clinically useful reference value. 71 normal volunteers(age, 19-65 years; 142 hands) examined who has no history of peripheral neuropathy, diabetic mellitus, chronic renal failure, endocrine disorders, anti-cancer medicine, anti-tubercle medicine, alcoholism, trauma, radiculopathy. Nicolet Viking II was use for detected terminal latency, amplitude of CMAP, conduction velocity and F-wave latency of median and ulnar motor nerve. Data analysis was performed using SPSS. Descriptive analysis was used for obtain mean and standard deviation, independent t-test was used to compare between Rt and Lt side also compare between different in genders. The results are summarized as follows: 1. Median motor nerve terminal latency was right 3.00ms, left 2.99ms and there was no significantly differences between right and left side and genders. 2. Median motor nerve amplitude of CMAP was right 17.26mV, left 1750mV and there was no significantly differences between right and left side and genders. 3. Median motor nerve conduction velocity was right 57.89m/sec, left 58.03m/sec and there was no significantly differences between right and left side and genders. 4. Median motor nerve F-wave latency was right 25.74ms, left 25.59ms and there was significantly differences between genders. 5. Ulnar motor nerve terminal latency was right 2.38ms, left 2.45ms and there was significantly differences between right and left side. 6. Ulnar motor nerve amplitude of CMAP was right 15.99mV, left 16.02mV and there was no significantly differences between right and left side and genders. 7. Ulnar motor nerve conduction velocity was right 60.35m/sec, left 59.73m/sec and there was no significantly differences between right and left side and genders. 8. Ulnar motor nerve F-wave latency was right 25.53ms, left 25.57ms and there was significantly differences between genders.

• Molecules and Cells
• /
• 제37권7호
• /
• pp.547-553
• /
• 2014

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권15호
• /
• pp.6463-6468
• /
• 2015

Background: Chemotherapy is one of the common approaches in treatment of cancers, especially leukemia. However, drug resistance phenomena reduce the likelihood of treatment success. Resveratrol is a herbal compound which through complicated processes makes some selected cells sensitive to treatment and induction of apoptosis. In the present study, the effects of resveratrol on the expression of miR 15a and miR16-1 and apoptosis in the CCRF-CEM cell line were investigated. Materials and Methods: The CCRF-CEM cell line was cultured under standard conditions and changes in miR 15a and miR 16-1 expression were analyzed by real time-PCR technique, with attention to reveratrol dose and time dependence. Also, apoptosis is evaluated by flow cytometry using annexin V and PI. Results: CCRF-CEM cells underwent dose-dependent apoptotic cell death in response to resveratrol. MiR 15a and miR 16-1 expression was up-regulated after 24 and 48 hours resveratrol treatment (p<0.05). Conclusions: The results of our study indicate that resveratrol induces apoptosis in a time and dose-dependent manner in CCRF-CEM cells. Also, increased expression level of miR 16-1 and miR 15a by means of resveratrol in CCRF-CEM cells might have a role in apoptosis induction and predisposition. According to our results resveratrol can be regarded as a dietary supplement to improve efficacy of anti-leukemia therapies.

• Journal of Ginseng Research
• /
• 제44권5호
• /
• pp.725-737
• /
• 2020

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and the PI3K/Akt/mTOR signaling pathway is activated in most patients with T-ALL and responsible for poor prognosis. 20(S)-Ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anticancer mechanisms of 20(S)-GRh2 targeting the PI3K/Akt/mTOR pathway in T-ALL have not been explored. Methods: Cell growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis, and autophagy. Results: In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at the G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species generation and upregulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, the PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in the spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. Conclusion: These findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.

• 한국약용작물학회지
• /
• 제25권5호
• /
• pp.322-327
• /
• 2017

Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with $80{\mu}M$ cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by $10{\mu}M$ doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicin-induced nephrotoxicity in an animal model.

• 한국환경농학회지
• /
• 제31권1호
• /
• pp.60-67
• /
• 2012

옻나무 주성분인 조추출액의 고추 탄저병균에 대한 항진균활성을 조사한 결과 1.0 mg urushiol/mL PDA 농도에서 18.3-39.5%의 억제효과가 있었으며, 푸른 고추에 병원성이 강한 것으로 조사된 GC계열의 균주보다는 DC계열의 균주에 대한 효과가 높았다. Urushiol의 농도가 1.0 mg/mL 일 경우 약 70% 정도의 포자가 발아한 PDB 용액에서보다 공시 모든 균주의 포자발아는 50% 이상 억제되었다. 동일한 농도에서 균사생장억제 효과 보다는 포자발아에 대한 억제 효과가 다소 높은 경향을 보였다. 푸른 고추와 붉은 고추에 옻 추출액을 처리하고 공시 탄저병균을 접종한 후 병 발생 억제효과를 in vitro에서 검정한 결과 붉은 고추에 DC 균주를 접종하였을 경우 1.0 mg/mL 농도 처리에서는 75.0%, 0.1 mg/mL 농도 처리에서는 58.0% 로 나타났으며, 푸른고추에 병원성이 강한 GC 균주를 접종하였을 경우에는 각각 68.1% 및 28.3% 탄저병 발생이 억제되었다. 비닐하우스에서 관행재배방법에 의해 고추를 재배하면서 고추 탄저병이 자연발생하기 시작한 8월 21부터 옻 추출액을 1주일 간격으로 3회 살포하고 최종 살포일 7일 후에 전체 고추 열매 중 이병 열매를 조사하여 옻 추출액의 병 발생 억제정도를 구한 결과 1차 조사한 9월 11일에는 무처리 대조구에 비해 옻 조 추출액을 1.0 mg/mL 처리한 시험구에서는 85.0% 탄저병 발생 억제효과를 보였으나, 0.01 mg/mL 처리구에서는 9.8%의 낮은 억제효과를 보였다. 9월 11일 조사 후 이병 열매를 모두 제거한 다음 동일한 방법으로 옻 추출액을 계속처리하고 10월 2일에 조사한 결과 1차 조사 시기보다 대조구의 이병과율이 훨씬 낮은 7.0% 였으며, 옻 추출액 처리효과는 공시 처리 농도별로 각각 60.0, 54.3 및 10.0%로 조사되었다.

• 한국응용과학기술학회지
• /
• 제36권3호
• /
• pp.766-778
• /
• 2019

본 연구에서는 초임계 공정에 의해 복령피를 추출하였고, 에탄올 복령피 추출물과 비교하여 항염, 미백, 항산화효과를 측정하였다. 또한 선정된 추출물의 제형과 약물전달 펩티드를 활용하여 효율적인 경피투과 방법을 제시하였다. 복령피의 항암, 항염성분으로 알려진 Pachymic acid를 지표성분으로 HPLC 분석 결과 에탄올 복령피 추출물 보다 초임계 복령피 추출물이 2배 이상 높게 추출되는 것으로 나타났다. 복령피의 항산화효과를 확인하기 위하여 DPPH 소거능과 ABTS 소거능은 복령피 에탄올 추출물이 초임계 복령피 추출물보다 더 낮은 농도에서 $IC_{50}$을 나타내었다. 하지만 RAW 264.7 세포 내 NO(Nitric oxide) 생성량을 측정한 결과에서는, 에탄올 복령피 추출물보다 초임계 복령피 추출물이 동일 농도에서 더 낮은 NO 생성량을 나타냈다. 또한 B16 melanoma 세포에 복령피 추출물을 $20{\mu}g/mL$ 농도를 72시간 처리 후 세포 내외 멜라닌 합성을 확인한 결과에서는, 에탄올 복령피 추출물과 초임계 복령피 추출물 모두 효과가 있었으며 초임계 추출물이 더 낮은 멜라닌 함량을 보였다. NO 생성량 실험에서 활용된 RAW 264.7 세포에서는 $800{\mu}g/mL$농도에서도 독성이 나타나지 않았다. 하지만 B16 melanoma 세포에서는 $50{\mu}g/mL$에서도 에탄올 추출물과 초임계 추출물 모두 60 % 미만의 생존율을 나타냈다. 초임계 복령피 추출물을 대상으로 리포좀 제형과 약물전달 펩티드를 활용하여 Franz diffusion cell 실험 결과에서는, 리포좀 제형과 약물 전달 펩티드가 초임계 복령피 추출물을 경피 투과를 증진시켜 주는 것으로 나타났다. 초임계 복령피 추출물이 다양한 효능의 화장품 소재로서 개발될 가능성이 있다고 판단된다.