• IMMUNE NETWORK
• /
• 제2권1호
• /
• pp.19-24
• /
• 2002

Background: Salvia miltiorrhiza (SM), a traditional oriental medicine, has been reported to have anti-tumor properties, but its exact mechanism remains to be elucidated. In this study, we investigated several of the molecular events that occur in human breast carcinoma MCF-7 cells and human pulmonary adenocarcinoma A549 cells. Methods: For this purpose, we evaluated the growth-inhibitory effect of SM in association with the expressions of p53, p21, cyclin D1, and pRb, which are known to be involved in cell cycle arrest. The extent of thymidine incorporation was also examined to assess G1/S phase cell cycle arrest in both cells by $^3H$-thymidine incorporation. Results: Our results show that SM inhibits the growth and the proliferation of MCF-7 and A549 cells. Furthermore, we also observed increased expression of p21 via a p53-dependent pathway in both cell lines after treating with SM. In addition, treatment with SM for 24 hours caused the suppression of hyperphosphorylated retinoblastoma protein (pRb) expression and the dephosphorylation of pRb. Conclusion: These findings suggest that the growth inhibitory and the anti-proliferation effects of SM on MCF-7 cells and A549 cells are mediated via the decreased expression and dephosphorylation of pRB by p21 up-regulation in a p53-dependent manner. To the best of our knowledge, this study is the first to report upon the molecular mechanisms involved in SM-induced tumor cell growth inhibition.

• 혜화의학회지
• /
• 제10권2호
• /
• pp.83-89
• /
• 2002

In the literatual study of anti-tumor effects of chunghwangsan for leukemia, the results were as follows. 1. Chunghwangsan is composed of Indigo naturalis and Realgar. The composing rate is 9 : 1 and it is made into capsule or piece. The basic administration is 0.3g per day and could increase the quantity each day. 2. The effects of Chunghwangsan is expelling toxin and colling, colling blood to detumescence, drying wetness and anticancer are. So it can be used to treat AML, CML and lymphoma. 3. The anticancer component of Indigo naturalis is indirubin which has the effects of suppression the transplanted tumor, activating the phagocyte of macrophage, promoting the maturation of myeloblast to improve cure rate of CML. The anticancer component of Realgar is $As_2O_3$ which has the direct cellular toxicity for leukemia cell. 4. In viewpoints of oriental medicine, leukemia is malignant myeloid neoplasia in which pathogen invade to shaoyin(少陰). So Chunghwangsan which is expelling toxin and colling, colling blood to detumescence, drying wetness and anticancer is effective to leukemia. 5. In clinical reports, Chunghwangsan is often used in CML, and also used in AML, lymphoma and so on. 6. Chunghwangsan is cool-natured, so we must carefully pay attention to pregnant women and hematsdthenic patients. The main side effects are nausea, bone marrow pain, diarrhea, polydefecation, hematokezia and purpora. We sometimes take invigorating stomach medicine to prevent the side effects. 7. If we continuously develop Chunghwangsan and therapy for leukemia with syndrome differentiation. we can improve the response and cure rate for leukemia in the future.

• Biomolecules & Therapeutics
• /
• 제17권2호
• /
• pp.138-143
• /
• 2009

We have reported previously on a replication incompetent recombinant adenoviral vector, AdLPCD, in which the expression of cytosine deaminase gene (CD) is driven by the tumor-specific L-plastin promoter. AdLPCD vector had been evaluated for its efficacy of chemosensitization of ovarian cancer cells to 5-FC. In spite of the fact that ovarian cancer cells, i.e., OVCAR-3 and SK-OV-3, are capable for adenoviral transduction judged by LacZ reporter gene analysis, two cell lines demonstrated quite different sensitivities toward AdLPCD/5-FC system. In OVCAR-3 cells, infection of AdLPCD followed by exposure to 5-FC resulted in the suppression of cell growth with statistical significance. On the other hand, SK-OV-3 cells were more resistant to the CD/5-FC strategy compared with OVCAR-3 cells under the same condition. The object of study was to investigate factors that would determine the sensitivity to AdLPCD/5-FC. We evaluated conversion rate of 5-FC to 5-FU after infection of AdLPCD by HPLC analysis, $IC_{50}$ of 5-FU, the expression level of integrin receptors i.e., ${\alpha}v{\beta}3$ and ${\alpha}v{\beta}5$, and status of p53 in OVCAR-3 and SK-OV-3 cells. The results indicated that OVCAR-3 cells have few favorable features compared with SK-OV-3 cells to be more effective to the AdLPCD/5-FC strategy; higher level of ${\alpha}v{\beta}5$ integrin, higher rate of conversion of 5-FC into 5-FC, and lower $IC_{50}$ of 5-FU. The results suggest that the replacement of 5-FU with CD/5-FC in combination chemotherapy would be less toxic and much greater cytotoxicity than the conventional combination chemotherapy in some patients.

• Journal of Digestive Cancer Research
• /
• 제4권1호
• /
• pp.1-9
• /
• 2016

The abundance of multi-drug resistance ATPase binding cassette and deranged self-renewal pathways shown in cancer stem cells (CSCs) played a crucial role in tumorigenesis, tumor resistance, tumor recurrence, and tumor metastasis. Therefore, elucidation of CSCs biology can improve diagnosis, enable targeted treatment, and guide the follow up of GI cancer patients. In order to achieve chemoquiescence, seizing cancer through complete ablation of CSCs, CSCs are rational targets for the design of interventions that will enhance responsiveness to traditional therapeutic strategies and contribute in the prevention of local recurrence as well as metastasis. However, current cancer treatment strategies fail to either detect or differentiate the CSCs from their non-tumorigenic progenies mostly due to the absence of specific biomarkers and potent agents to kill CSCs. Recent advances in knowledge of CSCs enable to produce several candidates to ablate CSCs in gastrointestinal (GI) cancers, especially cancers originated from inflammation-driven mutagenesis such as Barrett's esophagus (BE), Helicobacter pylori-associated gastric cancer, and colitis-associated cancer (CAC). Our research teams elucidated through revisiting old drugs that proton pump inhibitor (PPI) and potassium competitive acid blocker (p-CAB) beyond authentic acid suppression, chloroquine for autophage inhibition, sonic hedgehog (SHH) inhibitors, and Wnt/β-catenin/NOTCH inhibitor can ablate CSCs specifically and efficiently. Furthermore, nanoformulations of these molecules could provide an additional advantage for more selective targeting of the pathways existing in CSCs just like current molecular targeted therapeutics and sustained action, while normal stem cells intact. In this review article, the novel approach specifically to ablate CSCs existing in GI cancers will be introduced with the introduction of explored mode of action.

• International Journal of Stem Cells
• /
• 제16권3호
• /
• pp.315-325
• /
• 2023

Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

• 생명과학회지
• /
• 제27권8호
• /
• pp.958-964
• /
• 2017

Autophagy는 세포 내에서 세포의 재활용과 다양한 스트레스에 세포 homeostasis와 survival에 중요한 역할을 한다. 최근 연구에서는 autophagy 활성이 oncogenes과 tumor suppressor genes의 발현이 조절됨으로써 암이 발달되거나 억제됨이 보고되고 있다. Autophagy의 유도는 정상세포에서는 암 발생을 예방하는데 관여하며, 손상된 세포사멸 기능을 가진 암세포에서는 특정세포사멸기전을 유발하는데 중요한 역할을 한다. 또한 autophagy 억제는 항암약물과 치료법에 저항을 나타내는 암세포를 민감하게 만들어 치료효능을 증가시킨다고 증명되고 있다. 그러나 cancer 치료에서의 autophagy의 역할은 아직까지 완전히 이해되지 않았다. Oral squamous cell carcinoma(OSCC)는 구강암의 90% 이상을 차지하고 있으며, 전세계적으로 6th 가장 흔한 암중의 하나로, 최근 2배 이상 증가하고 있으며 높은 mortality rate를 보이고 있다. 구강암에서의 autophagy의 역할은 다른 암들과 마찬가지로 종양형성의 초기 단계 동안 종양억제성을 보이나, 종양진행 동안은 종양세포 생존에 관여하는 두 가지의 기능을 나타내는 것으로 보고되고 있다. 본 리뷰에서는, 암에서의 autophagy의 조절에 대한 다양한 역할을 요약하고, 이를 바탕으로 효과적인 암 치료를 위한 유망한 target으로 autophagy의 가능성을 제시하고자 한다.

• 한국식품과학회지
• /
• 제36권1호
• /
• pp.141-146
• /
• 2004

여러 발표에서 버섯추출물의 간접적 항종양효과에 대해 보고 되고 있다. 본 연구는 표고버섯의 직접적인 종양세포주 성장억제효과를 탐지하기 위하여 휴먼자궁경부암바이러스 타입 16의 종양유전자가 발현된 동물종양세포주(TC-1)를 이용하였다. 여러 추출용매 중 물을 이용한 추출액에서 TC-1 세포주의 성장억제효과를 탐지할 수 있었다. 이들 세포성장저해는 추출물첨가농도에 상응하며 $IC_{50}$는 $800\;{\mu}g/mL$로 계산되었다. 또한, 표고버섯 물 추출물은 휴먼자궁경부암세포주(CaSki and HeLa)에서도 유사한 세포성장억제효과를 보여 주었다. 첨가농도가 1.5 mg/mL에서는 첨가후 6시간째에 벌써 완전한 종양세포주(TC-1)의 성장억제가 탐지되었다. 이들 추출물을 열처리시 종양세포주성장억제가 소실되었으나 pH의 변화에서는 그대로 종양세포주성장억제효과가 탐지되었다. 이는 표고버섯 물 추출물 내에 있는 항종양물질이 열에 민감함을 의미한다. Annexin V 및 propidium iodide 염색에 의해 이들 TC-1종양세포주의 성장 억제효과는 apoptosis에 의해 매개됨을 보여 주었다 동물실험에서 표고버섯 물 추출물의 구강투여시 TC-1유래 종양의 성장 및 생성에 아무 효과를 주지 못하였다. 반면, 형성된 종양에 직접 주사시 종양크기의 감소가 탐지되었다. 요약하면 이들 연구에서 표고버섯 물 추출물에 존재하는 항암물질은 열에 민감하며 apoptosis에 의해 휴먼자궁경부암종양유전자에 의해 종양화된 세포주의 세포성장을 직접 억제하는 기능이 있음을 증명한다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권19호
• /
• pp.8019-8026
• /
• 2014

The promyelocytic leukemia (PML) gene is a gene known to be a tumor suppressor, although recent data suggest that it has a dual function in tumorigenesis. It was initially discovered in acute promyelocytic leukemia (APL) in which a t(15; 17) chromosomal translocation fused it to the retinoic acid receptor alpha ($RAR{\alpha}$). It has been shown to be involved in various types of cancer. It has at least 6 nuclear isoforms and a cytoplasmic type with different characteristics. Its multiple functions in growth inhibition, apoptosis induction, replicative senescence, inhibition of oncogenic transformation, and suppression of migration and angiogenesis have made it a therapeutic target for cancer therapy. However, its dual role in the process of tumorigenesis has made this field challenging. In this review, we discuss PML structure, functions and expression in tumors.

• 대한약침학회지
• /
• 제5권1호
• /
• pp.159-169
• /
• 2002

Objective: It will be examined in this research whether Lacquer poison can be used as an distinguished treatment to cure incurable diseases by considering literature existing and various papers. Method: I studies origin, alias, species, toxicity, effect, treatment, component, medical action and contraindication of Rhus vemiciflua stokes through various kinds literatures. Results: Sap of Rhus vemiciflua stokes that is used for medical purposes, has an effect on anti-tumor, anti-oxidation, hangover cure, and gastritis suppression. Even though urushiol and fIavonoids, the main ingredient of lacquer, has medical cure effects. but urushiol results in a dermatropic allergy. Sincc xylem of a Rhus vemiciflua stokes, however. does not induce the allergy but has medical efficacy, research on this topic is needed.

• BMB Reports
• /
• 제36권1호
• /
• pp.60-65
• /
• 2003

Cancer is frequently considered to be a disease of the cell cycle. As such, it is not surprising that the deregulation of the cell cycle is one of the most frequent alterations during tumor development. Cell cycle progression is a highly-ordered and tightly-regulated process that involves multiple checkpoints that assess extracellular growth signals, cell size, and DNA integrity. Cyclin-dependent kinases (CDKs) and their cyclin partners are positive regulators of accelerators that induce cell cycle progression; whereas, cyclin-dependent kinase inhibitors (CKIs) that act as brakes to stop cell cycle progression in response to regulatory signals are important negative regulators. Cancer originates from the abnormal expression of activation of positive regulators and functional suppression of negative regulators. Therefore, understanding the molecular mechanisms of the deregulation of cell cycle progression in cancer can provide important insights into how normal cells become tumorigenic, as well as how cancer treatment strategies can be designed.