• Title/Summary/Keyword: Cytotoxic therapy

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Biological Activities of the Essential Oil from Angelica acutiloba

  • Roh, Junghyun;Lim, Hyerim;Shin, Seungwon
    • Natural Product Sciences
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    • v.18 no.4
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    • pp.244-249
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    • 2012
  • Angelica acutiloba is one of the most intensively cultivated medicinal plants in Korea. The roots of this plant have been used as an important herbal drug, especially for the treatment of various female disorders, as the traditional therapy in Korea and other Asian countries. Consumption of its fresh leaves as a healthy vegetable has recently increased. In this study, essential oil fractions were extracted from the roots and leaves of this plant by steam distillation. Compositions of the two oils were compared by gas chromatography-mass spectrometry (GC-MS). The antibacterial activities of the essential oil were determined against three strains of Escherichia coli. DPPH radical scavenging and reducing power tests were performed to evaluateits antioxidant activities. The cytotoxic activities of the essential oil against a human breast and a uterine cancer cell line were estimated by MTT tests. Additionally, the morphological changes after treatment of the oil fraction were observed under a microscope. The essential oil fraction and its main components, Z-ligustilide and butylidene phthalide, inhibited the growth of three E. coli strains examined, with minimum inhibiting concentrations (MICs) ranging from 1.0 mg/ml to 8.0 mg/ml. Additionally, the essential oil fraction of A. acutiloba exhibited significant DPPH free radical scavenging activity and reducing power. Significant cytotoxic activities of the A. acutiloba essential oil were observed for human uterine (Hela) and breast (MCF-7) cancer cell lines.

Immune Checkpoint Inhibitors: Therapeutic Tools for Breast Cancer

  • Su, Min;Huang, Chun-Xia;Dai, Ai-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.905-910
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    • 2016
  • Breast cancer is one of the major threats to female health, and its incidence is rapidly increasing in many countries. Currently, breast cancer is treated with surgery, followed by chemotherapy or radiation therapy, or both. However, a substantial proportion of breast cancer patients might have a risk for local relapse that leads to recurrence of their disease and/or metastatic breast cancer. Therefore searching for new and potential strategies for breast cancer treatment remains necessary. Immunotherapy is an attractive and promising approach that can exploit the ability of the immune system to identify and destroy tumors and thus prevent recurrence and metastatic lesions. The most promising and attractive approach of immunotherapeutic research in cancer is the blockade of immune checkpoints. In this review, we discuss the potential of certain inhibitors of immune checkpoints, such as antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) and lymphocyte activation gene-3 (LAG-3), in breast cancer therapeutics. Immune checkpoint inhibitors may represent future standards of care for breast cancer as monotherapy or combined with standard therapies.

Menadione (Vitamin K3) Induces Apoptosis of Human Oral Cancer Cells and Reduces their Metastatic Potential by Modulating the Expression of Epithelial to Mesenchymal Transition Markers and Inhibiting Migration

  • Suresh, Shruthy;Raghu, Dinesh;Karunagaran, Devarajan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5461-5465
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    • 2013
  • Oral cancer is one of the most commonly occurring cancers worldwide, decreasing the patient's survival rate due to tumor recurrence and metastasis. Menadione (Vitamin K3) is known to exhibit cytotoxicity in various cancer cells but the present study focused on its effects on viability, apoptosis, epithelial to mesenchymal transition (EMT), anchorage independent growth and migration of oral cancer cells. The results show that menadione is more cytotoxic to SAS (oral squamous carcinoma) cells but not to non-tumorigenic HEK293 and HaCaT cells. Menadione treatment increased the expression of pro-apoptotic proteins, Bax and p53, with a concurrent decrease in anti-apoptotic proteins, Bcl-2 and p65. Menadione induced the expression of E-cadherin but reduced the expression of EMT markers, vimentin and fibronectin. Menadione also inhibited anchorage independent growth and migration in SAS cells. These findings reveal and confirm that menadione is a potential candidate in oral cancer therapy as it exhibits cytotoxic, antineoplastic and antimigratory effects besides effectively blocking EMT in oral cancer cells.

Cytotoxicity of Two Novel Cisplatin Analogues, $(CPA)_2Pt[DOLYM]$ and (DACH)Pt[DOLYM], to Human Cancer Cells In Vitro

  • Choi, Sang-Un;Kim, Kwang-Hee;Choi, Eun-Jung;Park, Sung-Hee;Kim, Kwan-Mook;Shon, Youn-Soo;Lee, Chong-Ock
    • Archives of Pharmacal Research
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    • v.22 no.2
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    • pp.151-156
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    • 1999
  • Despite the impressive antitumor activity of cisplatin, two major limitations of the drug, that is severe side effects and drug-resistance of cancer cells, make its use difficult of r cancer therapy. These limitations have resulted in a greate deal of effort having been expended into structural modifications of cisplatin. In this study, we tested two novel cisplatin analogues, (CPA)2 Pt[DOLYM] (COMP-I) and (DACH)Pt[DOLYM] (CoMP-II), for the mode of cytotoxic action against human tumor cells comparing with cisplatin and carboplatin in vitro. These two novel analogues had considerable cytotoxic activities against five kinds of human solid tumor cells, and especially COMP-II was more effective on HCT15 colon cancer cells than other compounds. In addition, COMP-II had cytostatic activity at low concentrations (10~0.3${\mu}g/ml$), but other compounds revealed little effect on tumor growth at the low concentration.

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Glyoxalase 1 as a Therapeutic Target in Cancer and Cancer Stem Cells

  • Ji-Young, Kim;Ji-Hye, Jung;Seung-Joon, Lee;Seon-Sook, Han;Seok-Ho, Hong
    • Molecules and Cells
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    • v.45 no.12
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    • pp.869-876
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    • 2022
  • Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential antitumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathionedependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

Anti-cancer Activity of Korean Local Plant Extracts Inducing Apoptosis in Various Carcinoma Cells (암세포 특이적 세포 사멸을 유도하는 자생식물 추출물의 항암 효과)

  • Yoon, Yi-Kwan;Lee, Seung-Eun;Lee, Dong-Jin;Rho, Mun-Chual;Sung, Jung-Suk;Park, Chung-Berm;Jang, Young-Joo
    • Korean Journal of Pharmacognosy
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    • v.40 no.1
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    • pp.6-12
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    • 2009
  • Thirty five methanol extracts from 19 natural local plants, which have been used as traditional anti-cancer medicine, were prepared. They were analyzed the cytotoxic effects on primary fibroblast cells and carcinoma cells. The root extract of Solanum nigrum were highly toxic in both cell lines with $IC_{50}$ values of less than $0.01{\mu}g/{\mu}l$, and 26 of 35 extracts were toxic in all cells with $IC_{50}$ values of $0.1{\sim}2{\mu}g/{\mu}l$. Three extracts including the fruit extracts of Solanum nigrum and Morus alba had no cytotoxic activity in both cell lines. Five of 35 extracts were highly toxic in cancer cells than in primary cells. Because primary cells were more resistant on these extracts, the five extracts were selected for anti-cancer agent candidates. Apoptosis or programmed cell death has an essential role in chemotherapy-induced tumor cell killing. Recently, inducers of apoptosis have been used in cancer therapy. When two of 5 cancer cell-specific cytotoxic extracts (Ulmus parvifolia and Zelkova serrata) were treated in concentration of $0.02{\sim}0.1{\mu}g/{\mu}l$, apoptosis were increased at 3-5 times in cancer cell lines. Finally, the apoptotic effects of these extracts were confirmed by cleavages of both poly-(ADP-ribose)-polymerase and caspase-3 as apoptotic markers. In this report, we suggested that two of 35 medicinal herb extracts can be useful anti-cancer drug candidates inducing apoptosis in several carcinoma cell lines.

Apoptotic Signaling Cascade of 5-aminolaevulinic Acid-based Photodynamic Therapy in Human Promyelocytic Leukemia HL-60 Cells

  • Nagao, Tomokazu;Matsuzaki, Kazuki;Takahashi, Miho;Minamitani, Haruyuki
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.509-511
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    • 2002
  • In this study, we investigated apoptotic cell death induced by photodynamic therapy using 5-aminolaevulinic acid (ALA-PDT) in human promyelocytic leukemia cells (HL-60). ALA-PDT induced apoptosis in HL-60 cells as confirmed by DNA agarose gel electrophoresis and nuclear staining with Hoechst 33342. The apoptotic cell death was inhibited by addition of broad-spectrum caspase inhibitor Z-Asp-CH$_2$-DCB, indicating that the apoptotic cell death was induced in a caspase-dependent manner. Actually, western blotting analysis revealed that caspase-3 was processed as early as 1.5 h after ALA-PDT. Cytoplasmic cytochrome c released from mitochondria was detected by western blotting. However, inhibitor of caspase-9, a cysteine protease located in the downstream of cytochrome c release, was not able to reduce the apoptotic cell death. Therefore, the mitochondrial apoptotic pathway was not involved in the ALA-PDT-induced apoptosis. On the other hand, it was found that ALA-PDT-induced apoptosis was clearly inhibited by pretreatment of caspase-8 inhibitor. These data suggest that caspase-8-mediated apoptotic pathway is important in ALA-PDT-induced cell death.

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Anti-effects of Photodynamic Therapy in Peroxiredoxin IV-induced AMC-HN3 Cell Lines

  • Ahn, Jin-Chul;Kang, Jung-Wook;Kim, Dae-Sik;Hong, Seong-No
    • Biomedical Science Letters
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    • v.14 no.4
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    • pp.263-267
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    • 2008
  • Photodynamic therapy (PDT) is a treatment utilizing the generation of singlet oxygen and other reactive oxygen species (ROS), which selectively accumulate in target cells. Peroxiredoxin (prx) plays an important role in eliminating peroxides generated during metabolism. Prx exert protective antioxidant role in cells though peroxidase activity. The aim of present work is to investigate the cytotoxicity of photofrin-mediated PDT in prx IV-transfectant AMC-HN3 cell lines. We confirmed that PDT has an effect on ROS generation in prx IV-induced cell lines. Treatment of PDT in prx IV-HN3 cell lines inhibits cytotoxic effects. Prx IV-induced HN3 cell lines resists in cell death during PDT. Also, prx IV-HN3 cell lines treated PDT inhibited ROS generation in contrast with vector control. We indicated that prx IV-induced AMC-HN3 cell lines have a function as inhibitors during PDT.

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CELLULAR AND MOLECULAR CHARACTERIZATION OF ADENOID CYSTIC CARCINOMA OF THE SALIVARY GLANDS (침샘 선양낭성암종의 세포학적, 분자생물학적 특성에 관한 연구)

  • Park, Young-Wook
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.27 no.2
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    • pp.110-122
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    • 2005
  • Adenoid cystic carcinoma (ACC) of salivary glands has a protracted clinical course with perineural invasion, delayed onset of hematogenous metastasis, and poor responses to classical cytotoxic chemotherapic agents. Most deaths from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the dissemination of metastatic cells is important for the design of more effective therapy of salivary cancer. I determined in vitro expression of epidermal growth factor receptor (EGFR) and its downstream effectors and vascular endothelial growth factor receptor (VEGFR)-2 on a human salivary ACC cell line (ACC2). I also evaluated the expression of EGF and VEGF signaling molecules and metastasis-related proteins on human salivary ACC cells orthotopically growing in nude mice. In Western blot and immunohistochemical analyses, EGFR and VEGFR-2 were presented and phosphorylated in ACC2 cells. In human parotid cancer xenografts in nude mice, EGF and VEGF signaling molecules, IL-8, and MMP-9 were expressed at markedly higher levels than in normal parotid tissues. Moreover, tumor-associated endothelial cells of this orthotopic parotid tumor expressed phosphorylated VEGFR-2 and phosphorylated Akt, which is a cell-survival protein. These data show that those biomarkers can be molecular targets for therapy of salivary ACC, which has a propensity for delayed lung metastasis.

Cancer Treatment Using Multiphoton Photodynamic Therapy

  • Zakir Hossain, S.M.;Golam Azam, S.M.;Enayetul Babar, S.M.
    • Molecular & Cellular Toxicology
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    • v.2 no.1
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    • pp.1-6
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    • 2006
  • Photodynamic therapy (PDT), a newly established treatment for solid tumors, involves the systemic administration of a tumor localizing photosensitizer that is only activated when exposed to light of appropriate wavelength. Photoactivation of photosensitizer in the presence of oxygen results in the formation of highly cytotoxic molecular species, which precipitates necrosis. PDT has now become a promising means for the treatment of cancer due to its specificity, relatively minimal side effects, and inexpensive. However, the application of PDT has been restricted to the treatment of superficial lesions or the use of interstitial light delivery. A single photon generally activates the photochemical reaction in traditional PDT. However the use of multi photon excitation, where two or more photons simultaneously excite a photosensitizer, allows for the use of wavelengths twice as long. Such wavelengths exhibit better transmittance through tissue and thereby deeper penetration is achieved. This paper will review theoretical principles of multi photon excitation, challenges associated with multi photon PDT and update the current and future role of multi photon PDT in cancer.