• BMB Reports
• /
• 제47권12호
• /
• pp.697-702
• /
• 2014

Recently, the interest in natural products for the treatment of cancer is increasing because they are the pre-screened candidates. In the present study, we demonstrate the therapeutic effect of celastrol, a triterpene extracted from the root bark of Chinese medicine on gastric cancer. The proliferation of AGS and YCC-2 cells were most sensitively decreased in six kinds of gastric cancer cell lines after the treatment with celastrol. Celastrol inhibited the cell migration and increased G1 arrest in cell-cycle populations in both cell lines. The treatment with celastrol significantly induced autophagy and apoptosis and increased the expression of autophagy and apoptosis-related proteins. We also found an increase in phosphorylated AMPK following a decrease in all phosphorylated forms of AKT, mTOR and S6K after the treatment with celastrol. Moreover, gastric tumor burdens were reduced in a dose-dependent manner by celastrol administration in a xenografted mice model. Taken together, celastrol distinctly inhibits the gastric cancer cell proliferation and induces autophagy and apoptosis.

• Journal of Ginseng Research
• /
• 제47권2호
• /
• pp.173-182
• /
• 2023

Cancer is a global public health issue that becomes the second primary cause of death globally. Considering the side effects of radio- or chemo-therapy, natural phytochemicals are promising alternatives for therapeutic interventions to alleviate the side effects and complications. Ginsenoside Rh2 (GRh2) is the main phytochemical extracted from Panax ginseng C.A. Meyer with anticancer activity. GRh2 could induce apoptosis and autophagy of cancer cells and inhibit proliferation, metastasis, invasion, and angiogenesis in vitro and in vivo. In addition, GRh2 could be used as an adjuvant to chemotherapeutics to enhance the anticancer effect and reverse the adverse effects. Here we summarized the understanding of the molecular mechanisms underlying the anticancer effects of GRh2 and proposed future directions to promote the development and application of GRh2.

• 생명과학회지
• /
• 제26권7호
• /
• pp.835-846
• /
• 2016

항암제 내성은 화학적 치료법의 가장 큰 난관의 하나로 효과적인 항암치료를 위해서 반드시 극복 되야 할 문제이다. ABCG2는 다약제 내성과 이를 특징으로 하는 암 줄기세포와의 연관성도 매우 높다고 보고되고 있다. 최근 암용해 바이러스가 다양한 암종과 항암제내성을 보이는 암 치료에 새로운 대안으로 대두되고 있다. 이에 본 연구에서는 항암제 내성 암 치료를 위해 새로운 암용해 백시니아 바이러스 SLJ-496을 개발하였다. 본 연구에서, cytophathic effect, plaque assay, viability assay를 통하여 야생형 바이러스에 비교하여 증가된 종양친화성을 확인하였다. 또한, invitro 환경에서 대장암 세포주(HT-29, HCT-116, HCT-8)를 비롯하여 위암 세포주(AGS, NCI-N87, MKN-28), 간암 세포주(SNU-449, SNU-423, SNU-475, HepG2) 그리고 난치성 암 종인 중피 세포종(NCI-H226, NCI-H28, MSTO-211h)에서 유의적인 세포독성효능을 입증하였다. ABCG2의 발현이 높은 HT-29세포의 3차원 구형배양을 통하여 ABCG2와 암줄기세포 특성의 연관성을 증명하였으며, 항암제 내성세포 모델에서 SLJ-496GFP가 유의한 세포독성을 나타내며 암세포내 복제능을 가지는 것을 입증하였다. ABCG2를 과발현 시킨 세포주 내 야생형 바이러스에 비교하여 유의적으로 낮은 세포 생존율을 증명하였으며, 바이러스의 복제능 또한 검증하였다. 또한, 지속적인 항암제 투여를 통하여 ABCG2의 발현이 높은 항암제 내성 세포주에서의 항종양 효능 또한 입증하였다. 이상의 결과를 토대로 ABCG2가 과발현 된 암 줄기세포 및 항암제 내성에 새로운 항종양 바이러스 SLJ-496 백시니아 바이러스 치료법이 새로운 치료 대안이 될 수 있을 것이라 제안한다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제29권5호
• /
• pp.315-322
• /
• 2003

Background : Important factors to determine treatment method and prognosis of oral cancer are anatomical site, tumor size, metastatic lesion, histologic cell differenciation and microvascular invasion. Anatomical site has great effect to oral cancer patient's survival rate because each site's accessibility and lymph node metastasis is different but this factor was't studied much than other factors. Patients and Methods : 228 patients with squamous cell carcinoma of common primary sites(Mandible, Maxilla, Floor of Mouth and Tongue) in oral cavity who were diagnosed in the Korea Cancer Center Hospital from January 1989 to December 1999, were clinically studied and analyzed on survival rate. Results : 1. Survival rates of each anatomical sites were Tongue(36.8%), Mandible(33.3%), Maxilla(28.7%) and Floor of Mouth(24.5%). Survival rates difference between Tongue and Floor of Mouth has significance(p<0.05). 2. Survival rates for early cancer of each site were Maxilla(100%), Mandible(57.1%), Tongue(54.2%) and Floor of Mouth(46.7%). Survival rates difference between Maxilla and Floor of Mouth has significance(p<0.05). 3. Survival rates by surgery method of each site were Maxilla(60.6%), Tongue(56.9%), Mandible(44.8%) and Floor of Mouth(26.3%). Survival rates difference between Maxilla and Floor of Mouth has significance(p<0.05). 4. Survival rates by radiation or chemo method of each site were Floor of Mouth(23.5%), Mandible(20.0%), Maxilla(9.5%), and Tongue(9.1%). Survival rates difference between each site doesn't have significance(p>0.05). 5. In advance stage, Survival rates by single therapy of each site were Tongue(33.6%), Mandible(23.5%), Floor of Mouth(16.7%), Maxilla(0%), and Survival rates difference between Maxilla and Tongue has significance (p<0.05). Survival rates by combination therapy of each site were Mandible(38.1%), Maxilla(30.0%), Floor of mouth(18.2%), Tongue(12.5%), and Survival rates difference between Mandible and Tongue has significance(p<0.05). Conclusion : Survival rate of tongue is higher than the other sites, early detection of oral cancer can increase survival rate at any site and combination therapy is the most effetive method, especially at maxilla.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권16호
• /
• pp.7025-7029
• /
• 2015

Background: The optimal sequence and extent of multimodality therapy remains to be defined for extrapulmonary small cell carcinoma because of its rarity. The purpose of our study was to assess the response to neoadjuvant chemotherapy followed by chemoradiation/radiation in patients with extrapulmonary small cell carcinoma. Materials and Methods: Four consecutively diagnosed patients were included in this study. The primary tumor site was oropharynx in three patients and esophagus in one. The patients with the limited disease were treated with chemotherapy followed by concurrent chemoradiation (n=2) or radiotherapy (n=1). The patient with the extensive disease with the primary site in vallecula was treated with chemotherapy and palliative radiotherapy to the metastatic site. Results: The median follow-up was 22.5 months (range, 8-24 months). Three patients with the limited disease (base of tongue, n=2; esophagus, n=1) were in complete remission. The patient with the extensive disease died of loco-regional tumor progression at 8 months from the time of diagnosis. Conclusions: The combination of chemotherapy and radiotherapy is the preferred therapeutic approach for patients with extrapulmonary small cell carcinoma. Induction chemotherapy followed by concurrent chemoradiation or radiation provides a good loco-regional control in patients with limited disease.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권2호
• /
• pp.699-704
• /
• 2012

Natural products have been the target for cancer therapy for several years but there is still a dearth of information on potent compounds that may protect normal cells and selectively destroy cancerous cells. The present study was aimed to evaluate the cytotoxic potential of n-butanolic leaf extract of $Annona$ $muricata$ L. on WRL-68 (normal human hepatic cells), MDA-MB-435S (human breast carcinoma cells) and HaCaT (human immortalized keratinocyte cells) lines by XTT assay. Prior to cytotoxicity testing, the extract was subjected to phytochemical screening for detecting the presence of compounds with therapeutic potential. Their relative antioxidant properties were evaluated using the reducing power and $DPPH^*$radical scavenging assay. Since most of the observed chemo-preventive potential invariably correlated with the amount of total phenolics present in the extract, their levels were quantified and identified by HPLC analysis. Correlation studies indicated a strong and significant (P<0.05) positive correlation of phenolic compounds with free radical scavenging potential. The results revealed that the extract was moderately cytotoxic to normal cells with a mean IC50 value of 52.4 ${\mu}g$ when compared with those obtained for cancerous cells (IC50 values of 29.2 ${\mu}g$ for MDA-MB-435S and 30.1 ${\mu}g$ for HaCaT respectively). The study confirms the presence of therapeutically active antineoplastic compounds in the n-butanolic leaf extract of $Annona$ $muricata$. Isolation of the active metabolites from the extract is in prospect.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권1호
• /
• pp.255-260
• /
• 2012

Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권18호
• /
• pp.8431-8438
• /
• 2016

Doxorubicin (DOX) was introduced as an effective chemotherapeutic for a wide range of cancers but with some severe side effects especially on myocardia. 2-Deoxy-D-glucose (2DG) enhances the damage caused by chemotherapeutics and ionizing radiation (IR) selectively in cancer cells. We have studied the effects of $1{\mu}M$ DOX and $500{\mu}M$ 2DG on radiation induced cell death, apoptosis and also on the expression levels of p53 and PTEN genes in T47D and SKBR3 breast cancer cells irradiated with 100, 150 and 200 cGy x-rays. DOX and 2DG treatments resulted in altered radiation-induced expression levels of p53 and PTEN genes in T47D as well as SKBR3 cells. In addition, the combination along with IR decreased the viability of both cell lines. The radiobiological parameter (D0) of T47D cells treated with 2DG/DOX and IR was 140 cGy compared to 160 cGy obtained with IR alone. The same parameters for SKBR3 cell lines were calculated as 120 and 140 cGy, respectively. The sensitivity enhancement ratios (SERs) for the combined chemo-radiotherapy on T47D and SKBR3 cell lines were 1.14 and 1.16, respectively. According to the obtained results, the combination treatment may use as an effective targeted treatment of breast cancer either by reducing the single modality treatment side effects.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권17호
• /
• pp.7037-7041
• /
• 2014

Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

• Journal of Korean Neurosurgical Society
• /
• 제50권5호
• /
• pp.434-440
• /
• 2011

Objective : The goals of surgical intervention for metastatic spinal cord compression (MSCC) are prolonging survival and improving quality of life. Non-ambulatory paraplegic patients, either at presentation or after treatment, have a much shorter life expectancy than ambulatory patients. We therefore analyzed prognostic factors for survival and postoperative ambulation in patients surgically treated for MSCC. Methods : We assessed 103 patients with surgically treated MSCC who presented with lower extremity weakness between January 2001 and December 2008. Factors prognostic for overall survival (OS) and postoperative ambulation, including surgical method, age, sex, primary tumor site, metastatic spinal site, surgical levels, Tokuhashi score, and treatment with chemo- or radiation therapy, were analyzed retrospectively. Results : Median OS was significantly longer in the postoperatively ambulatory group [11.0 months; 95% confidence interval (CI), 9.29-12.71 months] than in the non-ambulatory group (5.0 months; 95% CI, 1.80-8.20 months) ($p$=0.035). When we compared median OS in patients with high (9-11) and low (0-8) Tokuhashi scores, they were significantly longer in the former (15.0 months; 95% CI, 9.29-20.71 months vs. 9.0 months; 95% CI, 7.48-10.52 months; $p$=0.003). Multivariate logistic regression analysis showed that preoperative ambulation with or without aid [odds ratio (OR) 5.35; 95% CI 1.57-18.17; $p$=0.007] and hip flexion power greater than grade III (OR 6.23; 95% CI, 1.29-7.35; $p$=0.038) were prognostic of postoperative ambulation. Conclusion : We found that postoperative ambulation and preoperative high Tokuhashi score were significantly associated with longer patient survival. In addition, preoperative hip flexion power greater than grade III was critical for postoperative ambulation.