Artemisinin en kanker
Artemisinin is een anti-malaria middel
dat wordt ingezet wanneer gewone medicijnen niet meer helpen. Nu blijkt er ook een
mogelijke rol te zijn weggelegd voor deze plant bij de bestrijding van kankercellen maar
dit onderzoek staat nog in de kinderschoenen. De plant wordt al eeuwen door de Chinezen
gebruikt onder de naam qing hao (blue-green hao).
Uiteraard zet ik weer wat resources en
studies op een rijtje.
Ron
Oral artemisinin prevents and
delays the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer in
the rat.
Artemisinin, a compound isolated from the
sweet wormwood Artemisia annua L., has previously been shown to have selective toxicity
towards cancer cells in vitro. In the present experiment, we studied the potential of
artemisinin to prevent breast cancer development in rats treated with a single oral dose
(50mg/kg) of 7,12-dimethylbenz[a]anthracene (DMBA), known to induce multiple breast
tumors. Since artemisinin is a relatively safe compound that causes no known side effects
even at high oral doses, the present data indicate that artemisinin may be a potent cancer
chemoprevention agent.
PMID: 16356830. Lai H, Singh NP.
Department of Bioengineering, University of Washington, Box 357962, Seattle, WA
98195-7962, USA. hlai@u.washington.edu [Cancer Lett. 2006 Jan 8;231(1):43-8]
Artesunate in the treatment of
metastatic uveal melanoma--first experiences.
Artesunate (ART) is a derivative of
artemisinin, the active principle of the Chinese herb Artemisia annua L. Artesunate is
approved for the treatment of multidrug-resistant malaria and has an excellent safety
profile. It has been shown that Artesunate, apart from its anti-malarial activity, has
cytotoxic effects on a number of human cancer cell lines, including leukemia, colon cancer
and melanoma. We report on the first long-term treatment of two cancer patients with ART
in combination with standard chemotherapy. These patients with metastatic uveal melanoma
were treated on a compassionate-use basis, after standard chemotherapy alone was
ineffective in stopping tumor growth. The therapy-regimen was well tolerated with no
additional side effects other than those caused by standard chemotherapy alone. One
patient experienced a temporary response after the addition of ART to Fotemustine while
the disease was progressing under therapy with Fotemustine alone. The second patient first
experienced a stabilization of the disease after the addition of ART to Dacarbazine,
followed by objective regressions of splenic and lung metastases. This patient is still
alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a
median survival of 2-5 months. Despite the small number of treated patients, ART might be
a promising adjuvant drug for the treatment of melanoma and possibly other tumors in
combination with standard chemotherapy. Its good tolerability and lack of serious side
effects will facilitate prospective randomized trials in the near future.
Berger TG, Dieckmann D, Efferth T,
Schultz ES, Funk JO, Baur A, Schuler G. Department of Dermatology, University Hospital of
Erlangen, Erlangen, Germany. thomas.berger@derma.imed.uni-erlangen.de
Oncol Rep. 2005 Dec;14(6):1599-603.
Synergistic cytotoxicity of
artemisinin and sodium butyrate on
human cancer cells.
Butyric acid is a short chain fatty acid
produced by large bowel bacterial flora. It serves as an antiinflammatory agent and
nutrient for normal colon cells. Butyric acid has also been shown to induce apoptosis in
colon and many other cancer cells. Artemisinin is a compound extracted from the wormwood
Artemisia annua L. It has been shown to selectively kill cancer cells in vitro and to be
effective in treating animal and human cancer. We and others have found that the
artemisinin analog, dihydroartemisinin (DHA), kills cancer cells by apoptosis. In the
present study, the efficacy of a combined treatment of DHA and butyric acid at low doses
in killing cancer cells was investigated.
CONCLUSION: DHA in combination with
butyric acid acts synergistically at low doses. The combination may provide a less toxic,
inexpensive and effective cancer chemotherapy.
Singh NP, Lai HC. Department of
Bioengineering, Box 357962, University of Washington, Seattle, WA 98195-7962, USA. Narendra@u.washington.edu
Anticancer Res. 2005 Nov-Dec;25(6B):4325-31
PMID: 16309236
Dihydroartemisinin downregulates
vascular endothelial growth
factor expression and induces apoptosis in chronic myeloid
leukemia K562 cells.
Dihydroartemisinin (DHA), a more
water-soluble active metabolite of artemisinin derivatives, is safe and the most effective
antimalarial analog of artemisinin. In the present investigation, we assessed the effect
of DHA on vascular endothelial growth factor (VEGF) expression and apoptosis in chronic
myeloid leukemia (CML) K562 cells. The results demonstrated that in addition to its
antiproliferation effect on CML cells, DHA was also found to induce K562 cells apoptosis.
The percentage of apoptotic cells was increased to 6.9 and 15.8% after being treated with
5 and 10 micromol/l DHA for 48 h, respectively (P<0.001). The results from our study
together with its known low toxicity make it possible that DHA might present potential
antileukemia effect as a treatment for CML therapy, or as an adjunct to standard
chemotherapeutic regimens.
PMID: 16075280
Lee J, Zhou HJ, Wu XH. Department of
Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University,
Hangzhou, Zhejiang, 310031, PR China. Cancer Chemother Pharmacol. 2006 Jan;57(2):213-20.
Epub 2005 Aug 2
Publications Relating to Effects
of Artemisinin and its
Analogs on Cancer
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Berger TG, Dieckmann D, Efferth T, Schultz ES, Funk JO, Baur A, Schuler G. Artesunate in
the treatment of metastatic uveal melanoma--first experiences. Oncol Rep. 14(6):1599-1603,
2005.
Bhisutthibhan J, Philbert MA, Fujioka H, Aikawa M, Meshnick SR: The Plasmodium falciparum
translationally controlled tumor protein: subcellular localization and calcium binding.
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Chen HH, Zhou HJ, Fang X: Inhibition of human cancer cell line growth and human umbilical
vein endothelial cell angiogenesis by artemisinin derivatives in vitro." Pharmacol
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angiogenesis. Cancer Chemother Pharmacol. 53(5):423-432, 2004.
Chen HH, Zhou HJ, Wu GD, Lou XE. Inhibitory effects of artesunate on angiogenesis and on
expressions of vascular endothelial growth factor and VEGF receptor KDR/flk-1.
Pharmacology. 71(1):1-9, 2004.
Dell'Eva R, Pfeffer U, Vene R, Anfosso L, Forlani A, Albini A, Efferth T. Inhibition of
angiogenesis in vivo and growth of Kaposi's sarcoma xenograft tumors by the anti-malarial
artesunate. Biochem Pharmacol. 68(12):2359-2366, 2004.
Disbrow GL, Baege AC, Kierpiec KA, Yuan H, Centeno JA, Thibodeaux CA, Hartmann D, Schlegel
R. Dihydroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro
and in vivo. Cancer Res. 65(23):10854-10861, 2005.
Efferth T, Dunstan H, Sauerbrey A, et al: The anti-malarial artesunate is also active
against cancer. Int J Oncol 18:767-773, 2001.
Efferth T, Davey M, Olbrich A, et al.: Activity of drugs from traditional Chinese medicine
toward sensitive and MDR1- or MDR1-overexpressing multidrug-resistant human CCRF-CEM
leukemia cells. Blood Cells, Molecules, and Diseases 28:160-168, 2002.
Efferth T, Olbrich A, Bauer R: mRNA expression profiles for the response of human tumor
cell lines to the antimalarial drugs artesunate, arteether, and artemether. Biochem
Pharmacol 64:617-623, 2002.
Efferth T, Benakis A, Romero MR, Tomicic M, Rauh R, Steinbach D, Hafer R, Stamminger T,
Oesch F, Kaina B, Marschall M. Enhancement of cytotoxicity of artemisinins toward cancer
cells by ferrous iron. Free Radic Biol Med. 37(7):998-1009, 2004.
Efferth T. Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy. Drug
Resist Updat. 8(1-2):85-97, 2005.
Fishwick J, Edwards G, Ward SA, et al: Binding of dihydroartemisinin to differentiating
neuroblastoma cells and rat cortical homogenate. Neurotoxicology 19:405-412, 1998.
Fishwick J, Edwards G, Ward SA, et al: Morphological and immunocytochemical effects of
dihydroartemisinin on differentiating NB2a neuroblastoma cells. Neurotoxicology
19:393-403, 1998.
Hu YQ, Tan RX, Chu MY, et al: Apoptosis in human hepatoma cell line SMMC-7721 induced by
water-soluble macromolecular components of Artemisia capillaris Thunberg. Jpn J Cancer Res
91:113-117, 2000.
Huan-huan C, Li-Li Y, Shang-Bin L. Artesunate reduces chicken chorioallantoic membrane
neovascularisation and exhibits antiangiogenic and apoptotic activity on human
microvascular dermal endothelial cell. Cancer Lett. 211(2):163-173, 2004.
Jeyadevan JP, Bray PG, Chadwick J, Mercer AE, Byrne A, Ward SA, Park BK, Williams DP,
Cosstick R, Davies J, Higson AP, Irving E, Posner GH, O'Neill PM Antimalarial and
antitumor evaluation of novel C-10 non-acetal dimers of
10beta-(2-hydroxyethyl)deoxoartemisinin. J Med Chem. 47(5):1290-1298, 2004.
Jung M, Lee K, Kim H, Park M. Recent advances in artemisinin and its derivatives as
antimalarial and antitumor agents. Curr Med Chem. 11(10):1265-1284, 2004.
Jung M, Tak J, Chung WY, Park KK. Antiangiogenic activity of deoxoartemisinin derivatives
on chorioallantoic membrane. Bioorg Med Chem Lett. 2005 Dec 24; [Epub ahead of print]
Kim SJ, Kim MS, Lee JW, Lee CH, Yoo H, Shin SH, Park MJ, Lee SH. Dihydroartemisinin
enhances radiosensitivity of human glioma cells in vitro. J Cancer Res Clin Oncol.
132(2):129-135, 2006.
Lai H, Singh NP: Selective cancer cell cytotoxicity from exposure to dihydroartemisinin
and holotransferrin. Cancer Lett 91:41-46, 1995.
Lai H, Sasaki T, Singh NP, Messay A. Effects of artemisinin-tagged holotransferrin on
cancer cells. Life Sci. 76(11):1267-1279, 2005.
Lai H, Sasaki T, Singh NP Targeted treatment of cancer with artemisinin and
artemisinin-tagged iron-carrying compounds. Expert Opin Ther Targets. 9(5):995-1007, 2005.
Lai H, Singh NP. Oral artemisinin prevents and delays the development of
7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer in the rat. Cancer Lett.
231(1):43-48, 2006.
Lee CH, Hong H, Shin J, et al.: NMR studies on novel antitumor drug candidates,
deoxoartemisinin and carboxypropyldeoxoartemisinin. Biochem Biophys Res Comm 274:359-369,
2000.
Lee J, Zhou HJ, Wu XH. Dihydroartemisinin downregulates vascular endothelial growth factor
expression and induces apoptosis in chronic myeloid leukemia K562 cells. Cancer Chemother
Pharmacol. 57(2):213-220, 2006.
Li Y, Shan F, Wu JM, et al: Novel antitumor artemisinin derivatives targeting G1 phase of
the cell cycle. Bioorg Med Chem Lett 11:5-8, 2001.
Liu Y, Wong VK, Ko BC, Wong MK, Che CM. Synthesis and cytotoxicity studies of artemisinin
derivatives containing lipophilic alkyl carbon chains. Org Lett. 7(8):1561-1564, 2005.
McCarty MF. Turning an 'Achilles' Heel' into an asset--activation of HIF-1alpha during
angiostatic therapy will increase tumor sensitivity to iron-catalyzed oxidative damage.
Med Hypotheses. 61(4):509-511, 2003.
McLean WG, Ward SA: In vitro neurotoxicity of artemisinin derivatives. Med Trop (Mars)
58:28-31, 1998.
Moore JC, Lai H, Li JR, et al: Oral administration of dihydroartemisinin and ferrous
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Sadava D, Phillips T, Lin C, et al: Transferrin overcomes drug resistance to artemisinin
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Shaikenov TE, Adekenov SM, Williams RM, et al: Arglabin-DMA, a plant derived
sesquiterpene, inhibits farnesyltransferase. Oncol Rep 8:173-179, 2001.
Singh NP, Lai H: Selective toxicity of dihydroartemisinin and holotransferrin toward human
breast cancer cells. Life Sci 70:49-56, 2001.
Singh NP, Verma KB: Case report of a laryngeal squamous cell carcinoma treated with
artesunate. Arch Oncol 10:279-280, 2002.
Singh NP, Lai HC. Artemisinin induces apoptosis in human cancer cells. Anticancer Res.
24(4):2277-2280, 2004.
Singh NP, Lai HC. Synergistic cytotoxicity of artemisinin and sodium butyrate on human
cancer cells. Anticancer Res. 25(6B):4325-4331, 2005.
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Bron: Washington University
Meer studies mbt artemisinin
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