• Title/Summary/Keyword: Anticancer agent

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Cytotoxic Effects on HL-60 Cells of Myosin Light Chain Kinase Inhibitor ML-7 Alone and in Combination with Flavonoids

  • Lee, Joong-Won;Kim, Yang-Jee;Choi, Young-Joo;Woo, Hae-Dong;Kim, Gye-Eun;Ha, Tae-Kyung;Lee, Young-Hyun;Chung, Hai-Won
    • Toxicological Research
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    • v.25 no.4
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    • pp.181-188
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    • 2009
  • Uncontrolled cell growth and increased cell proliferation are major features of cancer that are dependent on the stable structure and dynamics of the cytoskeleton. Since stable cytoskeleton structure and dynamics are partly regulated by myosin light chain kinase (MLCK), many current studies focused on MLCK inhibition as a chemotherapeutic target. As a potent and selective MLCK inhibitor, ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1 H-hexahydro-1,4-diazapine hydrochloride] is a promising candidate for an anticancer agent, which would induce apoptosis as well as prevents invasion and metastasis in certain types of cancer cells. This study assessed cytotoxic effects of ML-7 against HL-60 cells and therapeutic efficacy of ML-7 as a potential antileukemia agent. Trypan-blue exclusion assays showed dose- and time- dependent decreases in ML-7 treated HL-60 cells (p<0.05). Comet assays revealed a significant increase in DNA damage in HL-60 cells after treatment with $40{\mu}M$ ML-7 for 2h. Sub-G1 fractions, analyzed by flow cytometry increased in a dose-dependent manner, suggesting that ML-7 can induce apoptotic cell death in HL-60 cells. ML-7 was selectively cytotoxic towards HL-60 cells; not affecting normal human lymphocytes. That selective effect makes it a promising potential anti-leukemia agent. In addition, anticancer efficacy of ML-7 in combination with flavonoids (genistein or quercetin) or anticancer drugs (cisplatin or Ara-C) against HL-60 cells was assessed. Combination of ML-7 with flavonoids increased the anti-cancer effect of ML-7 to a greater extent than combination with the anticancer drugs. This implies that ML-7 in combination with flavonoids could increase the efficacy of anticancer treatment, while avoiding side effects cansed by conventional anticancer drug-containing combination chemotherapy.

Anticancer Effect of Paedoksans for Oral Squamous Cell Carcinoma and Malignant Pleural Mesothelioma (패독산류의 구강편평세포암종 및 악성중피종에 대한 항암 활성)

  • Oh, Ha-Na;Kim, Hyun-Jung;Chae, Jung-Il;Shim, Jung-Hyun;Yoon, Goo
    • Korean Journal of Pharmacognosy
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    • v.48 no.3
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    • pp.213-218
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    • 2017
  • In order to search for anticancer agent as therapy of oral squamous cell carcinoma (OSCC) and malignant pleural mesothelioma (MPM) from Korean traditional prescriptions, we selected 58 traditional prescriptions based on a review of the Korean traditional medicine books. Among the selected traditional prescriptions, only water extracts of paedoksan (敗毒散) showed relatively good cytotoxicity at the concentration of $50{\mu}g/ml$. Additionally, we evaluated cytotoxicity for various paedoksans and each herbal ingredient in paedoksans. The root of Anthriscus sylvestris exhibited more cytotoxic effect than any other ingredients in paedoksans. Bioactivity-guided fractionation of the MC layer of Anthriscus sylvestris led to the isolation of deoxypodophyllotoxin (DPT). DPT exhibited dose-dependently significant cytotoxicity against OSCC and MPM cell with nM range. Therefore, DPT from A. sylvestris might be a potential candidate as an effective anticancer therapeutic agent for OSCC and MPM.

A Case Report of Partial Remission of Renal Cell Carcinoma with Multiple Liver Metastases Treated with Korean Herbal Medicine in Conjunction with Targeted Anticancer Therapy Afinitor (한약치료와 표적항암요법(아피니토)을 병행하여 부분 관해 된 신세포암 간전이 환자 1례)

  • Chang, Sung-Hwan;Park, Ji-Hye;Yoo, Hwa Seung
    • Journal of Korean Traditional Oncology
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    • v.22 no.2
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    • pp.13-24
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    • 2017
  • Objectives: The purpose of this study is to report the effect of Korean Herbal Medicine (KHM) on a Renal Cell Carcinoma with multiple liver metastases patient. Methods: One renal cell carcinoma with multiple liver metastases patient was treated by KHM in conjunction with targeted anticancer agent (Afinitor). The effect of KHM was measured by scanning with Computed Tomography (CT), Blood Test, Visual Analogue Scale (VAS) and Eastern Cooperative Oncology Group scale. Results: Multiple hepatic tumors were reduced after the treatment during 5 months (Partial Remission, PR). As treatment was performed, complications induced by targeted anticancer agent (Afinitor) were alleviated. Conclusions: This case provides us a possibility that Korean Herbal Medicine offers potential benefits for renal cell carcinoma with multiple liver metastases patient.

Base Specificity for DNA Interstrand Cross-Linking Induced by Anticancer Agent Bizelesin

  • Lee, Chong-Soon;Myung, Pyung-Keun;Gibson, Neil W.
    • Archives of Pharmacal Research
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    • v.19 no.3
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    • pp.191-196
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    • 1996
  • Bizelesin is a promising novel anticancer agent which is known to alkylate N3 of adenine to induce DNA interstrand cross-links (ISC) with in $5^I-TAATTA\; and\; 5^I-TAAAAAA$. We have investigated the base specificity for DNA ISC induced by bizelesin using oligomers containing the cross-linkable sequence $5^I-TAATTA\; and\; 5^I-TAAAAAA$. in which "N" was either A, C, G, or T. An analysis of denaturing polyacrylamide gel showed that bizelesin is able to induce DNA ISC in the duplex oligomer containing sequences $5^I-TAATTA\; and\; 5^I-TAAAAAA$. The formation of interstrand crosslinking did not occur in the sequences $5^I-TAATTA\; and\; 5^I-TAAAAAA$. DNA strand cleavage assay to determine the cross-linking site within $5^I-TAATTA$sequence showed that bizelesin alkylates guanine. These results demonstrate that bizelesin is able to induce DNA ISC at guanine but not at cytosine or thymine. In addition, guanine adducts have been found to be susceptible to DNA strand cleavage by exposure to hot piperidine. The extent of DNA strand cleavage, however, was not 100% efficient in either neutral pH buffer or hot piperidine.

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Metabolism of YH3945, a novel anticancer drug, in rats using 14C-labeled compound

  • Lee, Jae-Ick;Son, Jung-Hyun;Ahn, Byung-Nak;Lee, Bong-Yong;Kim, Dong-Hyun
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.130.1-130.1
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    • 2003
  • The metabolism of a novel anticancer agent 1-{3- [3-(4-Cyano -benzyl)-3H-imidazol-4-yl]-propyl }-3-(6-methoxy-pyridin-3-yl)-1-(2-trifluoromethyl-benzyl)-thiourea (YH3945) were investigated in the Sprague-Dawley rat after single oral and i.v. administration of [14C]-YH3945. Bile, feces, urine and plasma were collected and analyzed by an HPLC system equipped with multiple detectors. (omitted)

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Revisit to Unfulfilled Premise of Arylsulfonylimidazolidinones as Anticancer Agent

  • Hung, Dang-The;Lee, Jee-Hyun;Cho, Soo-Hyun;Hong, Chang-Yong;Jeong, Shin-Wu;Jeon , Ki-Wan;Lee, Sung-Bae;Choi, Whan-Geun;Jung, Sang-Hun
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.344.3-345
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    • 2002
  • For the development of novel anticancer agent. we have designed. synthesized. and tested novel 4-phenyl-1(N)-arylsulfonylimidazolidinones. As a result. much more potent cytotoxicities of these compounds against the various cancer cell lines than those of doxorubicin were demonstrated. Elaboration on aryl motif on sulfonyl moiety led us to find highly potent 4-phenyl-1-(N-acylindoline-5-sulfonyl)imidazolidinones. Among them, 4-phenyl-l- [N-(p-aminobenzoyl)indoline-5-sulfonyl]imidazolidinone (PA) was proved to have good pharmacological profile. (omitted)

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Cancer Chemopreventive Potential of Procyanidin

  • Lee, Yongkyu
    • Toxicological Research
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    • v.33 no.4
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    • pp.273-282
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    • 2017
  • Chemoprevention entails the use of synthetic agents or naturally occurring dietary phytochemicals to prevent cancer development and progression. One promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol that exhibits beneficial health effects including anti-inflammatory, antiproliferative, and antitumor activities. Currently, many preclinical reports suggest procyanidin as a promising lead compound for cancer prevention and treatment. As a potential anticancer agent, procyanidin has been shown to inhibit the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin has numerous targets, many of which are components of intracellular signaling pathways, including proinflammatory mediators, regulators of cell survival and apoptosis, and angiogenic and metastatic mediators, and modulates a set of upstream kinases, transcription factors, and their regulators. Although remarkable progress characterizing the molecular mechanisms and targets underlying the anticancer properties of procyanidin has been made in the past decade, the chemopreventive targets or biomarkers of procyanidin action have not been completely elucidated. This review focuses on the apoptosis and tumor inhibitory effects of procyanidin with respect to its bioavailability.