• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.658-666
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• 2021

Podophyllotoxin (PT), a lignan compound from the roots and rhizomes of Podophyllum peltatum, has diverse pharmacological activities including anticancer effect in several types of cancer. The molecular mechanism of the anticancer effects of PT on colorectal cancer cells has not been reported yet. In this study, we sought to evaluate the anticancer effect of PT on human colorectal cancer HCT116 cells and identify the detailed molecular mechanism. PT inhibited the growth of cells and colony formation in a concentration-dependent manner and induced apoptosis as determined by the annexin V/7-aminoactinomycin D double staining assay. PT-induced apoptosis was accompanied by cell cycle arrest in the G2/M phase and an increase in the generation of reactive oxygen species (ROS). The effects of PT on the induction of ROS and apoptosis were prevented by pretreatment with N-acetyl-L-cysteine (NAC), indicating that an increase in ROS generation mediates the apoptosis of HCT116 cells induced by PT. Furthermore, Western blot analysis showed that PT upregulated the level of phospho (p)-p38 mitogen-activated protein kinase (MAPK). The treatment of SB203580, a p38 inhibitor, strongly prevented the apoptosis induced by PT, suggesting that PT-induced apoptosis involved the p38 MAPK signaling pathway. In addition, PT induced the loss of mitochondrial membrane potential and multi-caspase activation. The results suggested that PT induced cell cycle arrest in the G2/M phase and apoptosis through the p38 MAPK signaling pathway by upregulating ROS in HCT116 cells.

• Journal of the Korean Society of Food Culture
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• v.36 no.2
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• pp.235-245
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• 2021

Lindera glauca Blume has been used in Korean traditional medicine to treat the symptoms of paralysis, abdominal pain, speech disorders, extravasations, contusions, and pain caused by rheumatoid arthritis. We investigated the effect of L. glauca Blume extracts on the proliferation of colorectal cancer cells in vitro using HCT116 human colorectal cancer cell lines. We also investigated its mechanism of action. For this purpose, we used the MTT assay, western blotting, DNA fragmentation analysis, and flow cytometry. HCT116 cells were cultured in several concentrations of ethanol extracts of L. glauca Blume root (0, 50, 100 ㎍/mL). In this study, colon cancer cell growth was inhibited by L. glauca Blume root extract in a dose-dependent manner. It was associated with induction of apoptosis as assessed by nuclear fragmentation and cell cycle analysis. Apoptosis was assessed using western blotting for TNF-α, IL-6, NF-κB, Caspase-3, PARP, Bax, Bcl-2, and SIRT1. The extract also dose-dependently upregulated the expression Bax, the pro-apoptotic gene and downregulated the expression of the anti-apoptotic gene Bcl-2. Furthermore, the extract enhanced Caspase-3 activity in a dose-dependent manner. Our findings provide evidence that L. glauca Blume extract may mediate its anti-proliferative effect via the modulation of apoptosis.

• Mass Spectrometry Letters
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• v.13 no.3
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• pp.84-94
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• 2022

Neoadjuvant chemoradiotherapy (nCRT) is a standard therapy used for locally advanced rectal cancer prior to surgery, which can more effectively reduce the locoregional recurrence rate and radiation toxicity compared to postoperative chemoradiotherapy. The response of patients to nCRT varies, and thus, robust biomarkers for predicting a pathological complete response are necessary. This study aimed to identify possible biomarkers involved in the complete response/non-response of rectal cancer patients to nCRT. Comparative proteomic analysis was performed on rectal tissue samples before and after nCRT. Proteins were extracted for label-free proteomic analysis. Western blot and real-time PCR were performed using rectal cancer cell line SNU-503 and radiation-resistant rectal cancer cell line SNU-503R80Gy. A total of 135 up- and 93 down-regulated proteins were identified in the complete response group. Six possible biomarkers were selected to evaluate the expression of proteins and mRNA in SNU-503 and SNU-503R80Gy cell lines. Lyso-phosphatidylcholine acyltransferase 2, annexin A13, aldo-ketose reductase family 1 member B1, and cathelicidin antimicrobial peptide appeared to be potential biomarkers for predicting a pathological complete response to nCRT. This study identified differentially expressed proteins and some potential biomarkers in the complete response group, which would be further validated in future studies.

• Journal of Life Science
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• v.26 no.6
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• pp.663-672
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• 2016

The Cnidium monnieri (L.) Cusson is an annual plant distributed in China and Korea. The fruit of C. monnieri is used as a medicinal herb that is effective for the treatment of carbuncle and pain in female genitalia. However, the anti-cancer effects of CME have not yet been reported. In this study, we assessed the apoptotic effects and cell cycle arrest effects of ethanol extracts from C. monnieri on HCT116 colon cancer cells. The results of an MTT assay and LDH assay demonstrated a decrease in cell viability and the cytotoxic effects of CME. In addition, the number of apoptotic body and the apoptotic rate were increased in a dose-dependent manner through Hoechst 33342 staining and Annexin V-PI double staining. In addition, cell cycle arrest occurred at the G1 phase by CME. Protein kinase B (Akt) plays an important role in cancer cell survival, growth, and division. Akt down-regulates apoptosis-mediated proteins, such as mammalian target of rapamycin (mTOR), p53, and Glycogen Synthase kinase-3β (GSK-3β). CME could regulate the expression levels of p-Akt, p-mTOR, p-GSK-3β, Bcl-2 family members, caspase-3, and PARP. Furthermore, treatment with CME, LY294002 (PI3K/Akt inhibitor), BIO (GSK-3β inhibitor), and Rapamycin (mTOR inhibitor) showed that apoptotic effects occurred through the regulation of the AKT/mTOR/GSK-3β signaling pathway. Our results demonstrated CME could induce apoptosis and cell cycle arrest in HCT116 colon cancer cells.

• Journal of Dairy Science and Biotechnology
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• v.26 no.1
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• pp.5-10
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• 2008

This study was conducted to isolate protein components from culture supernatant of Lactobacillus casei. and measure anti-cancer activity. The protein components were isolated A and B on Ultrafiltration membrane(3, 10, 30, 100 KDa). And the protein components A and B were isolated fractions(number $3{\sim}9$) on FPLC. Experimental studies were progressed through the cell cytotoxicity and anti-cancer activities. Cell cytotoxicity test using human kidney normal cell(293) showed cytotoxicity of below 20% by the protein components A and B($100{\mu}g/mL$). The anti-cancer activity was increased up to 70% by the protein components A and B($100{\mu}g/mL$) in AGS(stomach cancer), A549(lung cancer), MCF-7 (breast cancer), SK-OV-3(ovary cancer) and LoVo(colon cancer). Cell cytotoxicity test was showed cytotoxicity of about 50% by the fractions(number 3, 8, 9) isolated FPLC. The others have not the cytotoxicity about the human normal cell. The anti-cancer activity was increased up to 70% by the fraction number 7 in cancer cell line. Therefore the components isolated from culture supernatant of Lactobacillus casei were showed anti-cancer activity.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.5 no.1
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• pp.1-17
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• 1999

Large bowel cancer shows the 4-5th frequency in cancers that occurs in Korea. The western medicine cures the Large bowel cancer by radiation, surgery and chemotherapy. While, Oriental medicine cures the Large bowel cancer by Herb-drugs, acupuncture, moxa and et al. With just one way of treating Large bowel cancer can't be effective remedy. Because each medicine has a strength and weakness, it is effective treatment when two medicine combines and supplement each other. We got the following result about a trend of oriental and western combination treatment for Large bowel cancer through studding records. 1. In Large bowel cancer, colon cancer is referred hematochezia(腸風下血), rectal cancer is refereed enterotoxin(腸毒), and anal cancer is accumulation of pathogens in yin(結陰). 2. The western medicine treats Large bowel cancer patient with surgery first. They need on assembly treatment such as chemical, radiation and immune treatment. In oriental medicine, they treats Large bowel cancer patients with differentiation of symptom and signs and treatment(辨證施治) for example, insufficiency of spleen and stomach(脾胃虛弱), collapse of the spleen-ql(脾氣下陷), stagnation of blood stasis and toxic agent(瘀毒內結), reinforcing both qi and blood(脾血下陷), stagnation of damp-phlegm(痰濕凝結) and cure for them by acupuncture and moxa too. 3. In combination with oriental and western medical treatment princple of Large bowel cancer by each stage is as follows. First stage is cured with radical surgery and herb-drugs without chemotherapy. The intermediate and terminal stage patients is used radiation before surgery, or after palliative surgery cour with chemotherapy, radiation and Herb-drugs. In terminal stage patients, unable for surgery, is used combination between chemotherapy, palliative radiation and Herb-drugs. 4. After radiation surgery, the terminal stage patients who have extensively lymph node metastasis or local contraindication is able to undergo combination of Herb-durgs and chemotherapy. 5. The cure-effect with oriental and western medicine combination treatment was better than that just with oriental or western medical treatment. 6. The merits of oriental and western medicine combination treatment lengthen one's life and diminish the bad effect of chemotherapy and complete radiation treatment, prevent from relapsing, maintain the balance in their environment of body and improve immunity.

• Journal of Life Science
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• v.32 no.3
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• pp.263-269
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• 2022

Cancer cachexia-anorexia is a multi-organ metabolic syndrome characterized by anorexia and weight loss. Generally, such symptoms are a serious problem in cancer patients, adversely affecting chemotherapy success and survival rate. Cachexia has been reported to accompany up to 80% of gastrointestinal cancers, such as pancreatic, lung, and colon cancer, though it is relatively rare in lymphoma or breast cancer patients. It is also known that cancer-induced anorexia occurs independently of chemotherapy, although decreased appetite due to chemotherapy is well reported. In terms of pathoflammatory cytokines that are excessively increased by tumor tissues. Since the mechanism of cancer cachexia is not yet fully understood, there are currently no therapeutic agents or diagnostic markers to treat it. A recently published study identified a substance secreted from cancer cells that induces cancer anorexia, and the molecular mechanism causing the eating disorder was discovered. An increase in the expression of this substance has been shown to be statistically correlated with the symptoms of cachexia in cancer patients, and it is therefore expected to be applicable in the diagnosis and development of therapeutic agents for cancer cachexia. This review article aims to provide an overview of the key molecular mechanisms of the anorexia and tissue wasting caused by cancer cachexia.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.7
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• pp.839-845
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• 2009

Colorectal cancer is the third most common malignant neoplasm in the world. Much attention has been focused on reducing colon cancer risk through medical properties of natural compound that could act as anticarcinogens. In this study, we evaluated the antioxidant and antigenotoxic effects of Styela plicata (S. plicata) from in vitro experiments. S. plicata extracts showed antioxidant activity measured by TRAP assay and antigenotoxic effect in $200{\mu}M$ $H_2O_2$ induced DNA damage in human leukocytes. Especially, freeze-dried S. plicata extracted with methanol showed the highest level of TRAP (0.225 mM) and inhibition of DNA damage (66.8%). Additionally we observed the effect of S. plicata on the formation of aberrant crypt foci (ACF) induced by dimethylhydrazine (DMH) and DMH induced DNA damage (by comet assay) in male SD rats. The animals were divided into three groups and fed high-fat and low fiber diet (100 g lard+20 g cellulose/kg diet) without (normal control and DMH control) or with a 3% (w/w) of lyophilized S. plicata powder (DMH+S. plicata). One week after beginning the diets, rats were treated with DMH (30 mg/kg, s.c.) for 6 weeks except for normal control group, which was treated saline instead; dietary treatments were continued for the entire experiment. Nine weeks after DMH injection, administration of S. plicata resulted in reduction of ACF numbers, to 82.7% of the carcinogen control value ($7.67{\pm}2.04$ vs. $1.33{\pm}0.53$: p<0.01). S. plicata supplementation induced antigenotoxic effect on DMH-induced DNA damage in the blood cell (% tail intensity: $6.79{\pm}0.26$ vs. $6.13{\pm}0.22$). These data indicate that S. plicata extract has antigenotoxic and anticarcinogenic effects from in vitro experiments and S. plicata exerts a protective effect on the process of colon carcinogenesis, possibly by suppressing the DMH-induced DNA damage in blood cell and the development of preneoplastic lesions in colon.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6585-6590
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• 2013

Background: Although FOLFOX (infusional fluorouracil/leucovorin plus oxaliplatin) is established as a standard chemotherapeutic regimen, the long term efficacy of adjuvant XELOX (oral capecitabine plus intravenous oxaliplatin) in Asian colorectal cancer (CRC) patients remains anecdotal. Moreover, uncertainties persist as to whether pharmacogenetic differences in Asian populations preclude equally tolerable and effective administration of these drugs. Method: One hundred consecutive patients with resected colorectal cancer received adjuvant XELOX (oxaliplatin 130 $mg/m^2$ on day 1 plus capecitabine 900 $mg/m^2$ twice daily on day 1 to 14 every 3 weeks for 8 cycles) at Queen Mary Hospital, Hong Kong. Endpoints monitored during follow-up were disease-free survival (DFS) and disease recurrence, overall survival (OS) and adverse events (AEs). Results: The median patient age was 56 years, 56% were diagnosed with rectal cancer and 44% with colonic cancer. After a median follow-up of 4.3 years (95% confidence interval, 3.2-4.7), 24 recurrences were confirmed including 13 patients who died due to progressive disease. Four-year DFS was 81% in colon cancer patients and 67% in rectal cancer patients (p=0.06 by log-rank test). For the cohort as a whole, OS was 90% at 3 years and 84% at 5 years. Treatment-related AEs led to early withdrawal in four patients. The commonest non-hematological AEs were neuropathy (91%), hand-foot syndrome (49%) and diarrhea (46%), while the commonest grade 3/4 AEs were neutropenia (11%) and diarrhea (10%). Conclusion: These results confirm the favourable long term survival benefit with good tolerability in using adjuvant XELOX in treating East Asian colorectal cancer patients.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.514-522
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• 2004

Background : Non-steroidal anti-inflammatory drugs (NSAID) are useful in chemoprevention of colorectal cancers. Continuous NSAID administation causes 40% to 50% reduction in relative risk for colorectal cancer. Sulindac possesses an antiproliferative effect and induces apoptosis and tumor regression on colon cancer and other types of cancers. We intended to analyze the effects of sulindac in three non-small cell lung cancer cell lines. Materials and Methods : The human lung cancer cell lines, A549, NCI-H157 and NCI-H460 were used for this study. Viability was tested by MTT assay, and cell death rate was measured by lactate dehydrogenase(LDH) release. Apoptosis was estimated by flow cytometric analysis and nuclear staining. Results: Sulindac was able to decrease the viability of non-small cell lung cancer cells in a dose- and time- dependent manner. In a parallel effect of sulindac on cell death rate, LDH release was increased in sulindac-treated lung cancer cells. Sulindac significantly increased apoptosis characterized by an increase of $sub-G_0/G_1$ fraction and morphological change of nuclei. The rate of apoptotic cells after sulindac treatment in lung cancer cells increased in a time- and dose- dependent manner in flow cytometric analysis. Apoptotic cells were defined as nuclear shrinkage, chromatin condensation and nuclear fragmentation of cells. Conclusion : Sulindac decreases viability and induces the apoptosis of lung cancer cells. Further studies will be needed to elucidate the potential mechanism of sulindac-induced apoptosis in lung cancer cells.