S-allylcysteine (SAC) is an aged garlic derived water soluble organosulfur compound and has been suggested to have anticarcinogenic activity against diverse types of cancer cells. This review summarizes the cellular signaling pathways and molecular mechanisms whereby SAC exerts its effects on cellular proliferation, apoptosis, cell cycle progression and metastasis based on the results from both in vitro and in vivo studies. SAC activates proapoptotic proteins including Bax and caspase-3, but suppresses antiapoptotic Bcl-2 family proteins to bring about cancer cell death through mitochondria-mediated intrinsic pathway. SAC also inhibits cellular proliferation by inducing cell cycle arrest in which SAC reduces expression and activation of NF-κB, cyclins, Cdks, PCNA and c-Jun, but elevates expression of cell cycle inhibitor proteins p16 and p21 through suppression of both PI3K/Akt/mTOR and MAPK/ERK signaling pathways. And, SAC inhibits invasion and metastasis of cancer cells by inducing suppression of both angiogenesis and epithelial-mesenchymal transition (EMT) through decreased cyclooxygenase (COX)-2 expression and increased E-cadherin expression which were then caused by suppression of inhibitory transcription factors Id-1 and SLUG from SAC-mediated inactivation of both MAPK/ERK and PI3K/Akt/mTOR/NF-κB signaling pathways. Furthermore, SAC prevents toxic compound-induced carcinogenesis by inducing antioxidant enzymes such as glutathione-s-transferase (GST). Thus, SAC can be considered as a potential chemotherapeutic agent for the prevention and treatment of cancer.
Lung cancer is a type of cancer that has the highest mortality rate. It is mainly classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Chemotherapy is used to treat lung cancer, but long-term treatment causes side effects and drug resistances. Curcumin is a bright yellow polyphenol extracted from the root of turmeric. It has biological activities, such as anti-oxidant, anti-cancer, and anti-inflammatory effects. In this study, we observed differential cell death in human lung cancer cells. Based on the results, curcumin at 10, 30, and 50 μM exhibited a dose-dependent inhibition on the cell survival of several lung cancer cells, with minor differential phenotypes. In addition, apoptosis, autophagy, and reactive oxygen species (ROS) regeneration were observed through flow cytometry. Curcumin dose-dependently increased these phenotypes in A549 (NSCLC) and DMS53 (SCLC), which were restored by corresponding inhibitors. Western blotting was performed to measure the level of expression of apoptosis- and autophagy-related proteins. The results indicate that Bax, PARP, pro-caspase-3, and Bcl-2 were dose-dependently regulated by curcumin, with seemingly higher Bax/Bcl-2 ratios in DMS53. In addition, autophagic proteins, p-AKT, p62, and LC3B, were dose-dependently regulated by curcumin. ROS inhibition by diphenyleneiodonium reduced the induction of apoptosis and autophagy generated by curcumin. Taken together, it is suggested that curcumin induces apoptosis and autophagy via ROS generation, leading to cell death, with minor differences between human lung cancer cells.
Purpose : This study was to evaluate the effectiveness of preoperative radiotherapy in maxillary sinus cancer. Materials and Methods : A retrospective analysis was done for 42 patients with maxillary sinus cancer who were treated with radiation with or without surgery from April 1986 to September 1996. There were 27 male and 15 female patients. Patients' age ranged from 24 to 75 years (median 56 years). Stage distribution showed 2 in T2, 19 in T3, and 21 in T4 lesions The histologic type was squamous cell carcinoma in 38, undifferentiated carcinoma in 1, transitional cell carcinoma in 1, and adenoid cystic carcinoma in 2 patients. All patients were treated with radiation initially with a dosage range of 50.4-70.2 Gy (median 70.2 Gy) before further evaluation of remnant disease. Eleven patients were given induction chemotherapy (2cycles of 5-fluorouracil and cisplatin) concurrently with radiotherapy. Six to eight weeks after radiotherapy with or without chemotherapy computerized tomography (CT) of paranasal sinus was taken to evaluate remnant disease. If the CT finding showed remnant disease, a Caldwell-Luc procedure was done to get the specimen of suspicious lesions. A radical maxillectomy was done if the specimen was proven to contain malignancy. In contrast periodic follow-up examination was done without any radical surgery if the tissue showed only granulation tissue. Follow-up period ranged from 3 to 92 months with a median 16 months. Results : Nine (21.4$\%$) patients showed complete response (CR) and 33 patients (78.6$\%$) showed persistent disease (PER) to initial radiotherapy. Among the 9 CR patients, 7 patients had no evidence of disease (NED), 1 patient had local failure, and 1 patient had regional failure. Among 33 PER patients, salvage total maxillectomy was done in 10 patients, and the surgery was not feasible or refused in 23 patients. Following the salvage radical surgery, 2 patients were NED and 8 patients were PER status. Overall and disease- free survival rate at 5 years was 23.1$\%$ and 16.7$\%$, respectively. The only factors associated with the overall survival rate was the response to radiotherapy (P<0.01). Conclusion : The only factors associated with the overall survival rate was the response to radiotherapy. We could omit a radical mutilating surgery by preoperative irradiation in 7 of 42 patients (21.4$\%$) so as to preserve their facial integrity.
Journal of the Korean Society of Food Science and Nutrition
/
v.40
no.5
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pp.619-624
/
2011
Tea extract (TE) has been shown to have anti-tumor properties in a wide variety of experimental systems. We evaluated green tea extract (GTE) as a biochemical modulator for the antitumor activity of cisplatin and doxorubicin in the treatment of human lung cancer A549 cells. Cells were grown in RPMI-1640 medium supplemented with 10% (v/v) heat-inactivated fetal bovine serum and two antibiotics (100 units/mL penicillin and $100\;{\mu}g$/mL streptomycin). Two types of TE, epigallocatechin galate (EGCG) and GTE, were used in this experiment. The cells were seeded at $1{\times}10^4$ cells/well in the RPMI-1640 media with or without TE ($100\;{\mu}g$/mL) and then treated with different concentrations of doxorubicin ($0{\sim}14\;{\mu}g$/mL) or cisplatin ($0{\sim}35\;{\mu}g$/mL). After incubation in 5% $CO_2$ at $37^{\circ}C$ for 24 hr, cell viability was determined with a MTT assay. We used a Western blot to detect the influence of EGCG and GTE on the expression of p53 and caspase-3 genes in the A549 cells. A549 cell viability decreased to 15% with a $10\;{\mu}g$/mL concentration of cisplatin, and to 21% with a $8\;{\mu}g$/mL concentration of doxorubicin, as measured with the MTT assay. However, pre-treatment of the cells with EGCG ($100\;{\mu}g$/mL) or GTE ($100\;{\mu}g$/mL) resulted in decreased cell viability with $6\;{\mu}g$/mL of cisplatin and $4\;{\mu}g$/mL of doxorubicin. There was no apparent change in cell viability between EGCG or GTE administration in cisplatin- or doxorubicin-induced cytotoxicity in A549 cells. The levels of p53 and caspase-3 in the A549 cells increased with both EGCG and GTE treatment. We found that GTE could potentially affect cisplatin- or doxorubicin-induced cytotoxicity of A549 cells, which may be useful in the chemotreatment of cancer.
Kim, So Young;Hong, Su Hyun;Choi, Sung Hyun;Cheong, JaeHun;Choi, Yung Hyun
Journal of Life Science
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v.30
no.5
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pp.460-467
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2020
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in the word. Although radiation and chemotherapy are generally effective, there are various side effects that greatly limit the effectiveness of these treatments. Therefore, traditional herbs may have potential as important resources for the discovery of liver cancer therapeutics. In this study, we selected three Korean herbal medicine formulas from the Donguibogam, namely Bigihwan (BGH), Daechilgithang (DCGT), and Mokwhyangbinranghwan (MHBRH), and evaluated their anti-cancer effects on HCC cells. According to our results of three ethanol extracts, BGH was more effective at suppressing HCC growth than DCGT or MHBRH. Furthermore, flow cytometry analysis showed that inhibition of HCC proliferation by the three extracts was associated with the induction of apoptosis and autophagy. In particular, BGH significantly increased mitochondrial impairment and showed the possibility of inducing mitophagy in comparison with the other two extracts. BGH prominently upregulated the levels of microtubule-associated protein light chain-3 which was accompanied by a decrease in the expression of anti-apoptotic Bcl-2 without altering the expression of pro-apoptotic Bax. In addition, the levels of PTEN-induced kinase 1 were also markedly increased in BGH-treated HCC cells. Moreover, autophagy blocking improved cell viability and reduced apoptosis after the three treatments, indicating that autophagy by these extracts enhances HCC cells against cytotoxicity. In conclusion, our findings show that BGH demonstrates the highest anti-cancer activity among the three formulas and inhibits the proliferation of HCC cells through autophagy induction.
The sprig of Jinryungtang Gagambang has been used for curing as a traditional medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Jinryungtang Gagambang extract against cancer, and to study some mechanisms responsible for its effect. The cytotoxic and antitumor effects were evaluated on human cell liens (A549, hep3B, Caki-1, Sarcoma 180) after exposure to Jinryungtang Gagambang extract using in ILS, colony forming efficency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. As a result of exposure to Jinryungtang Gagambang extract, the proliferation of A549, hep3B, Caki-1, good correlations were shown from the results of SRB assay and those of clogenetic assay. 2. The oral administration of Jinryungtang Gagambang extract showed significant effects of increase of MST(mean survival time) and ILS(increased life span) depending on the increasing concentration. 3. Against squamous cell carcinoma induced by MCA, Jinryungtang Gagambang decreased not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Jinryungtang Gagambang also significantly suppressed the development of 3LL cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Jinryungtang Gagambang extract into TBM. 4. Jinryungtang Gagambang extract also increased NK cell activities. According to the above results, it could be suggested that Jinryungtang Gagambang extract has prominent antiutmor effect.
Kim, Do-Yoon;Yu, Ho-Jin;Yoon, Mi-So;Park, Joo-Hoon;Jang, Sang-Hee;Lee, Hwan-Myung
Journal of Life Science
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v.22
no.9
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pp.1224-1230
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2012
Cancer chemotherapy drugs command a large share of the market, and the development of new therapeutics with high efficacy and specificity is an active area of study. Recently, the development of cancer therapeutics from natural products targeting angiogenesis has drawn attention due to conventional chemotherapeutics showing serious side effects and resistance in cancer cells. In this study, we investigated the pharmacological efficacy of Gomisin A, an active ingredient of Schizandra chinensis baillon, on tumor growth and metastasis. Administration of Gomisin A at 10 and 100 ${\mu}g/ml$ reduced tumor growth in vivo by $80.5{\pm}8.1%$ and $96.2{\pm}2%$, respectively, compared with positive tumor controls. Treatment of Gomisin A in normal and various tumor cell lines did not exert significant toxicity. Mice treated with Gomisin A at a concentration of 10 and 100 ${\mu}g$/head showed a significant reduction in tumor-induced angiogenesis of $151{\pm}16.9%$ and $98.5{\pm}29.5%$, respectively. Furthermore, tumor metastasis analysis revealed that the administration of Gomisin A at a concentration of 10 and 100 ${\mu}g$/head inhibited tumor metastasis by $13.5{\pm}8.56%$ and $58.3{\pm}9.12%$, respectively. In addition, Gomisin A significantly decreased cell adhesion of the B16BL6 cells to the extracellular matrix. These results demonstrate that Gomisin A inhibits tumor growth via suppression of angiogenesis and tumor metastasis inhibition, without cellular toxicity. The pharmacological efficacy of Gomisin A suggests that it may be a potential candidate for the development of cancer drugs.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.30
no.6
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pp.509-515
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2004
Photodynamic therapy(PDT) has advanced to clinical trials for the treatment of a variety of solid tumors and presents an alternative treatment option for tumors resistant to chemo-and/or radio-therapy. PDT is based on the combination of laser light of appropriate wavelength and energy to activate a systemically or locally applied photosensitizer that concentrates preferentially in malignant tissues. In this study, phototoxicity of laser EIT 21 was analysed in human osteosarcoma cell(HOS) and the second objective of this study was to determine the ability of laser EIT 21 to induce apoptosis. This study demonstrated that laser EIT 21 had a phototoxicity to HOS cells. In order to examinate whether cell death was induced by necrosis or apoptosis, variety of techniques which assess apoptosis were used. TUNEL assay showed only a few the positive reaction on condensed nuclei. It is hard to find condensed or fragmented nuclei on HOS cells irradiated with laser EIT 21 in Hemastat and AO/EB stain. By DNA electrophoresis, cells also did not show DNA degradation characteristic of apoptosis with a ladder pattern of DNA fragments. Apoptosis-related factors were analyzed by western blotting. The expression of p53 was constant and cells irradiated with laser did not show the caspase-3 and PARP degradation, therefore we suggest that p53 and caspase-3 are not involved in laserinduced cell death.
In the course of our search for compounds effective to multidrug-resistant cancer cells from myxobacteria with the adriamycin-resistant cancer cell line CL02, we found cytotoxic activity against the CL02 cells in culture extract of Sorangium cellulosum JW1045. Activity-guided fractionation of the culture extract led to the isolation of an active principle, chivosazole F, This compound showed high cytotoxic activity against cultured human cancer cells. The $IC_{50}$ values, measured by a SRB assay with different cell lines, ranged from 0.1 to 10 ng/ml. Furthermore chivosazole F was as active against drug-resistant cancer cells CL02 and CP70 as against the corresponding sensitive cells.
Mariah Kim;Seyeon Lee;Kibeom Ku;Irang Nam;Minhwa Kim;So-yeon Kim
The Journal of Internal Korean Medicine
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v.44
no.5
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pp.1092-1100
/
2023
Introduction: We present a case of multiple myeloma with amyloidosis, which has features of peripheral neuropathy after induction chemotherapy before autologous peripheral blood stem cell transplantation, in a 56-year-old woman with Korean medicine. Case Presentation: For 17 days of hospitalization, the patient with complaints of numbness and a tingling sensation in the hands and feet was treated with acupuncture, herbal medicine. To reduce the symptoms, we provided Korean medicine treatments, including herbal medicine, acupuncture, and moxibustion. The Visual Analog Scale (VAS) was used to evaluate the results of the treatment. Until discharge, the VAS scores decreased for both hands and the foot tingling sensation. Conclusion: According to these results, Korean medicine treatment may be considered an effective treatment for tingling sensations in a patient with multiple myeloma with amyloidosis. Prospective studies are needed in the future to confirm and expand these findings.
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