• Journal of Yeungnam Medical Science
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• v.10 no.2
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• pp.432-444
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• 1993

Multidrug resistance(MDR) phenotype is frequently observed in animal and human cancer cell lines selected for in vitro resistance to a single chemotherapeutic agent. It is characterized by the diminished drug accumulation and is related to the drug efflux mechanism in resistant cells. In the present study, adriamycin resistant cells(L1210-$AdR_6$ : $10^{-6}M$ adriamycin, $-AdR_5$ : $10^{-5}M$) and vincristine resistant cells (L1210-$VcR_7$ : $10^{-7}M$ vincristine, $-VcR_6$ : $10^{-6}M$) were produced from mouse lymphoblastic leukemia cell line L1210. Growth profiles of survived cells were observed for 5 days with MTT(thiazolyl blue) assay and resistance was compared with $IC_{50}$(drug concentration of 50% survival reduction in absorbance). Resistant cells proliferated more slowly than sensitive cell. Doubling times were 29.7hr in L1210, 68.7hr in L1210-$AdR_5$ and 58.2hr in $-VcR_6$. MDRs expressed as resistance factor were as follows, L1210-$AdR_5$ was 76.4 times for vincristine, L1210-$VcR_6$ was 96.4 times for adriamycin. The cell membrane proteins with three different M.W. were recognized to be related resistance, 220, 158, and 88 kd in L1210-$AdR_5$, 158, 140 and 88 kd in L1210-$VcR_6$ by SDS-PAG electrophoresis. Cell surface membrane proteins were identified by radio-iodination and autoradiogram, their molecular weights were 158, 72.8, and 42.4 Kd in L1210-$VcR_6$.

• Korean Journal of Plant Resources
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• v.33 no.4
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• pp.279-286
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• 2020

Purple loosestrife-Lythrum anceps (Koehne) Makino is a herbaceous perennial plant belonging to the Lythraceae family. It has been used for centuries in Korea and other Asian traditional medicine. It has been showed pharmacological effects, including anti-oxidant and anti-microbial effects. However, the mechanisms underlying its anti-cancer effect are not yet understood. In this study, we investigated the mechanism of apoptosis signaling pathways by ethanol extract of Lythrum anceps (Koehne) Makino (ELM) in human leukemia U937 cells. Treatment with ELM significantly inhibited cell growth in a dose-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies (ApoBDs), DNA fragmentation and increased populations of sub-G1 ratio. Induction of apoptosis by ELM was connected with up-regulation of death receptor (DR) 4 and DR5, pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 protein, and inhibitor of apoptosis protein (IAP) family proteins, depending on dosage. This induction was associated with Bid truncation, mitochondrial dysfunction, proteolytic activation of caspases (-3, -8 and -9) and cleavage of poly(ADP-ribose) polymerase protein. Therefore, our data indicate that ELM suppresses U937 cell growth by activating the intrinsic and extrinsic apoptosis pathways, and thus may have applications as a potential source for an anti-leukemic chemotherapeutic agent.

• Journal of Life Science
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• v.25 no.12
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• pp.1384-1392
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• 2015

Sagantang (SGT), a Korean multiherb formula comprising six medicinal herbs, Paeonia lactiflora Pall., Belamcanda chinensis (L.) DC, Gardenia jasminoides Ellis, Poria cocos Wolf, Cimicifuga heracleifolia Komarov, and Artractylodes japonica Koidzumi, was recorded in “Dongeuibogam.” The present study investigated the anticancer potential of SGT in AGS human gastric carcinoma cells. The results indicated that SGT treatment significantly inhibited the growth and viability of AGS cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, in addition to chromatin condensation and DNA fragmentation, and the accumulation of annexin-V positive cells. The induction of apoptotic cell death by the SGT treatment was associated with up-regulation of Fas protein expression, truncation of Bid, and down-regulation of the anti-apoptotic Bcl-2 protein. The SGT treatment also effectively induced the loss of mitochondrial membrane potential, which was associated with the activation of caspases (caspase-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase. However, a pan-caspase inhibitor significantly blocked the SGT-induced apoptosis and growth suppression in AGS cells. This study suggests that SGT induces caspase-dependent apoptosis through an extrinsic pathway by upregulating Fas, as well as through an intrinsic pathway by modulating Bcl-2 family members in AGS cells. The results suggest that SGT may be a potential chemotherapeutic agent for the control of human gastric cancer cells. However, further studies will be needed to confirm the potential of SGT in cancer prevention and therapy in an in vivo model and to identify biological active compounds of SGT.

• Journal of Life Science
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• v.23 no.3
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• pp.389-398
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• 2013

Platycodin D is a major constituent of triterpene saponins, which is found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. Several pharmacological effects of this compound have been reported recently, such as anti-inflammation, immunogenicity, anti-adipogenesis, lowered cholesterol, and anti-cancer activity. However, the mechanism by which this action occurs is poorly understood. In this study, we found that platycodin D greatly increased the potential of the anti-proliferative effect in various cancer cell lines. Our data revealed that platycodin D treatment resulted in a time- and concentration-response growth inhibition of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation of cells in the sub-G1 phase. Apoptosis induction of U937 cells by platycodin D correlated with an increase in the Bax/Bcl-2 ratio and caused the down-regulation of IAP family members. In addition, platycodin D treatment resulted in proteolytic activation of caspase-3, the concomitant degradation of poly(ADP-ribose) polymerases, and the collapse of the mitochondria membrane potential (${\Delta}{\Psi}_m$). However, the cytotoxic effects induced by platycodin D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrated the important role that caspase-3 played in the observed cytotoxic effect. These findings suggest that platycodin D may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells. These findings also provided important new insights into possible molecular mechanisms of the anti-cancer activity of platycodin D.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1178-1187
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• 1998

Background : Recently the incidence of tuberculosis is increasing in many countries and control of the disease is further threatened by the emergence of multi-drug resistant tuberculosis. So rapid detection of drug resistance is very important. Pyrazinamide (PZA) is a first-line chemotherapeutic agent for tuberculosis. Now in Korea, we perform PZase activity test instead of actual pyrazinamide susceptibility test for the detection of PZA resistant M. tuberculosis. Recently the pncA gene, encoding the PZase of M. tuberculosis, was completely sequenced. And it was reported that the mutation of pncA gene would be associated with PZA resistance of M. tuberculosis. Therefore we performed this study to evaluate the possibility for the rapid detection of PZA resistant M. tuberculosis using PCR-SSCP of pncA gene. Method : 44 cultured clinical isolates of M. tuberculosis, BCG Tokyo strain. BCG French strain, and one M. bovis isolate were studied. We used H37Rv as the reference strain, The PZase activity test was done at the reference laboratory of Korean Tuberculosis Institute. DNA was extracted by bead-beater method and 561 bp fragment including pncA gene was amplified by PCR. The PCR product were digested by BstB I enzyme. SSCP was done using MDE gel. Of the 44 strains of M. tuberculosis, 22 strains were PZase-positive and other 22 strains were PZase negative. Results : Of the 22 PZase positive strains, 18 strains(82%) showed the same mobility compared with that of H37Rv and 4(18%) showed different mobility. Of the 22 PZase-negative strains, 19(86%) strains showed the same mobility pattern compared with that of H37Rv and 3(14%) showed different mobility. Naturally PZA-resistant BeG-French strain, BCG-Tokyo strain, and one M. bovis isolate showed the same band pattern each other, but their mobility were different from that of H37Rv. The results of PZase activity test and PCR-SSCP of pncA of M. tuberculosis were statistically significantly correlated each other (p<0.01). Conclusion : The PCR-SSCP after BstB I restriction of pncA gene of M. tuberculosis may be a useful method for the rapid detection of PZA-resistant M. tuberculosis.

• Korean Journal of Plant Resources
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• v.32 no.4
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• pp.255-263
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• 2019

Glycyrrhizae radix is one of the most frequently prescribed ingredients in Oriental medicine, and Glycyrrhizae radix extract has been shown to exert anti-cancer effects. However, the cellular and molecular mechanisms of programed cell death (apoptosis) by Glycyrrhizae radix are poorly defined. In the present study, it was examined the molecular mechanisms of apoptosis by water extracts of Glycyrrhizae radix (GRW) in human bladder T24 cancer cells. It was found that GRW could inhibit the cell growth of T24 cells in a concentration-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, DNA fragmentation and increased populations of annexin-V positive cells. The induction of apoptotic cell death by GRW was connected with an up-regulation of pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic proteins (Bcl-2 and Bcl-xL), and inhibition of apoptosis family proteins (XIAP, cIAP-1 and cIAP-2). In addition, apoptosis-inducing concentrations of GRW induced the activation of caspase-9, an initiator caspase of the mitochondrial-mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of PARP. GRW also induced apoptosis via a death receptor-mediated extrinsic pathway by caspase-8 activation, resulting in the down-regulation of total Bid and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. Taken together, the present results suggest that GRW may be a potential chemotherapeutic agent for the control of human bladder cancer cells.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.35-41
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• 1998

Purpose : To investigate the role of adjuvant chemoradiotherapy in adenocarcinoma of the rectum, we retrospectively compared the treatment results between postoperative adjuvant radiotherapy alone and combined chemoradiotherapy. Material and Methods : From October 1989 to May 1994, 141 patients with rectal carcinoma were treated by postoperative adjuvant therapy in Yonsei Cancer Center. Sixty eight patients were treated by radiation therapy alone. Seventy three patients were treated by combined chemoradiotherapy. Radiation therapy was delivered with 10 MV linear accelerator, 180cGy fraction/5 days per week. Total radiation doses were 5400cGy in the postoperative radiotherapy alone group. Three to twelve cycles of Fluorouracil(mean dose $393.9mg/m^2$) with Leucovorin($20mg/m^2$) and 5040cGy of radiation were delivered in the combined chemoradiotherapy group. Third and 4th cycle of chemotherapy were administrated during the radiation treatment in the combined group. The median follow up was 38 months with a range of 3 to 81 months. Results : The 5 year overall survival rate of radiation alone group and combined group were $60.1\%$ and $66.3\%$, respectively. The 5 year disease free survival rate of radiation aione group and combined group were $54.2\%$ and $65.5\%$, respectively There was no significant difference of overall survival and disease free survival between RT alone group and combined group(p<0.05). But the 5 year Local failure free survival rate of combined group was significantly better than radiotherapy alone group($05.8\%\;vs.\;50.3\%.\;p=0.04$). Conclusion : There was no significant difference in overall survival, disease free survival, and distant metastasis free survival between postoperative adjuvant radiotheray alone group and combinded chemoradiotherapy group. Only the Local failure free survival rate was superior in the combined treatment group. These results confirm the radiosensitizing effect of the chemotherapeutic agent in the combined chemoradiotherapy treatment.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.79-92
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• 2007

[ $\underline{Purpose}$ ]: For the first time, a nationwide survey in the Republic of Korea was conducted to determine the basic parameters for the treatment of esophageal cancer and to offer a solid cooperative system for the Korean Pattern of Care Study database. $\underline{Materials\;and\;Methods}$: During $1998{\sim}1999$, biopsy-confirmed 246 esophageal cancer patients that received radiotherapy were enrolled from 23 different institutions in South Korea. Random sampling was based on power allocation method. Patient parameters and specific information regarding tumor characteristics and treatment methods were collected and registered through the web based PCS system. The data was analyzed by the use of the Chi-squared test. $\underline{Results}$: The median age of the collected patients was 62 years. The male to female ratio was about 91 to 9 with an absolute male predominance. The performance status ranged from ECOG 0 to 1 in 82.5% of the patients. Diagnostic procedures included an esophagogram (228 patients, 92.7%), endoscopy (226 patients, 91.9%), and a chest CT scan (238 patients, 96.7%). Squamous cell carcinoma was diagnosed in 96.3% of the patients; mid-thoracic esophageal cancer was most prevalent (110 patients, 44.7%) and 135 patients presented with clinical stage III disease. Fifty seven patients received radiotherapy alone and 37 patients received surgery with adjuvant postoperative radiotherapy. Half of the patients (123 patients) received chemotherapy together with RT and 70 patients (56.9%) received it as concurrent chemoradiotherapy. The most frequently used chemotherapeutic agent was a combination of cisplatin and 5-FU. Most patients received radiotherapy either with 6 MV (116 patients, 47.2%) or with 10 MV photons (87 patients, 35.4%). Radiotherapy was delivered through a conventional AP-PA field for 206 patients (83.7%) without using a CT plan and the median delivered dose was 3,600 cGy. The median total dose of postoperative radiotherapy was 5,040 cGy while for the non-operative patients the median total dose was 5,970 cGy. Thirty-four patients received intraluminal brachytherapy with high dose rate Iridium-192. Brachytherapy was delivered with a median dose of 300 cGy in each fraction and was typically delivered $3{\sim}4\;times$. The most frequently encountered complication during the radiotherapy treatment was esophagitis in 155 patients (63.0%). $\underline{Conclusion}$: For the evaluation and treatment of esophageal cancer patients at radiation facilities in Korea, this study will provide guidelines and benchmark data for the solid cooperative systems of the Korean PCS. Although some differences were noted between institutions, there was no major difference in the treatment modalities and RT techniques.