Abstract
A series of low molecular compounds from Chinese herbal medicines which have proved to be, in some cases, highly effective especially in tumor therapy, is listed here (part II will deal with high molecular compounds, to be published in the next issue). In contrast to synthetic agents used in cancer chemotherapy, these natural compounds have relatively low toxicities. Many of the clinical studies referred to in this paper have been carried out on Asians. Because genetic factors influence enzyme levels, sometimes leading to striking differences in metabolism and pharmacokinetics of drugs, results obtained in clinical studies carried out in China are not 100 % transferable to the European population. The mechanisms of action of these compounds are manifold, consisting of reactions with DNA bases, intercalation in DNA, inhibition of topoisomerases, inhibition of protein kinases, induction of apoptosis etc. Some of the compounds have interesting structural features, that may be used as lead structures for the development of further antitumor agents.
Key words
Antitumor agents - Chinese herbal medicines - low molecular natural compounds - traditional Chinese medicine
References
-
1
Owen T Y, Wang S Y, Chang S Y, Lu F L, Yang C L, Hsu B.
A new antitumor substance - lycobetaine (AT-1840).
Ko Hsueh Tung Pao.
1976;
21
285-7
-
2
He H M, Weng Z Y.
Structure-activity relationship study of the new anticancer drug lycobetaine (AT-1840).
Acta Pharmaceutica Sinica.
1989;
24
302-4
-
3 Xu B. Pharmacologic study of several anticancer agents of natural origin. Proceedings of Intern Summit on Drugs from Natural Products. October 9 - 12, 1995 Beijing, China; Vol 1
-
4
Ghosal S, Singh S K, Kumar Y, Unnikrishnan S, Chattopadhyay S.
Chemical constituents of Amaryllidaceae. XXVI. The role of ungeremine in the growth-inhibiting and cytotoxic effects of lycorine: evidence and speculation.
Planta Medica.
1988;
54
114-6
-
5
Wang X W, Yu W J, Shen Z M, Yang J L, Xu B.
Cytotoxicity of hydroxycamptothecin and four other antineoplastic agents on KB cells.
Acta Pharmacologica Sinica.
1987;
8
86-90
-
6
Wu Y L, Wu Y X, Yu C S, Zhang S Y, Su Z C, Jiang S J.
The cytocidal effect of AT-1840 and parvovirus H-1 on gastric cancer cells.
Shanghai Medical Journal.
1988;
11
683-8
-
7
Liu J, Yang S L, Xu B.
Characteristics of the interaction of lycobetaine with DNA.
Acta Pharmacologica Sinica.
1989;
10
437-42
-
8
Liu J, Yang S L, Xu B.
Effects of lycobetaine on chromatin structure and activity of murine hepatoma cells.
Science in China Series B.
1990;
33
1459-65
-
9
Chen J Z, Chen K X, Jiang H L, Lin M W, Ji R Y.
Theoretical investigation on interaction binding of analogs of AT-1840 to double-stranded polynucleotide.
Progress in Natural Science.
1997;
7
329-35
-
10
Wang P, Shi G B, Song G Q, Chen K X, Ji R Y.
Assignment of proton resonances and conformational characterization of oligodeoxyribonucleic acid d(CCGTACGG) in solution.
Acta Biochimica and Biophysica Sinica.
1996;
28
703-5
-
11
Gan L, Liu X J, Chen K L, Ji Y Y.
Computer simulation on the interaction between antitumor agent lycobetaine and DNA.
Gaojishu Tongxun.
1992;
2
30-3
-
12
Barthelems H U, Niederberger E, Roth T, Schulte K, Tang W C, Zankl H, Fiebig H H, Eisenbrand G, Marko D.
Lycobetaine acts as a selective topoisomerase IIβ poison and inhibits the growth of human tumor cells.
British Journal of Cancer.
2001;
85
1585-91
-
13
Zhang S Y, Lu F L, Yang J L, Wang L J, Xu B.
Effect on animal tumors and toxicity of lycobetaine acetate.
Acta Pharmacologica Sinica.
1981;
2
41-5
-
14
Hua D H, Saha S, Takemoto D J.
Anticancer activities of 2,5,8,9-substituted 6-oxo-1,2,3,4,5,6-hexahydrophenanthridines on multi-drug-resistant phenotype cells.
Anticancer Research.
1997;
17A
2435-41
-
15 Niederberger E. Mechanismus-orientierte Untersuchungen zur antineoplastischen Wirkung von Naturstoffen und Naturstoff-Derivaten. Thesis, Universtiy of Kaiserslautern Germany; 1998
-
16 Schulte K. Synthese von Phenanthridin- und Benzo[c]phenanthridin-Derivaten und Untersuchungen auf ihre biologische Wirkung. Thesis, Universtiy of Kaiserslautern Germany; 2000
-
17
Kushida N, Atsumi S, Koyano T, Umezawa K.
Induction of flat morphology in K-ras-transformed fibroblasts by lycorine, an alkaloid isolated from the tropical plant Eucharis grandiflora
.
Drugs under Experimental and Clinical Research.
1997;
23
151-5
-
18
Fang S D, Wang L K, Hecht S M.
Inhibitors of DNA topoisomerase I isolated from the roots of Zanthoxylum nitidum
.
Journal of Organic Chemistry.
1993;
58
5025-7
-
19 The Pharmacopoeia of the People’s Republic of China. Vol I Ed 2000 Chemical Industrial Press Beijing, PR China;
-
20
Colombo M L, Bosisio E.
Pharmacological activities of Chelidonium majus L. (Papaveraceae).
Pharmacological Research.
1996;
33
127-34
-
21
Stermitz F R, Gillespie J P, Amoros L G, Romero R, Stermitz T A, Larson K A, Earl S, Ogg J E.
Synthesis and biological activity of some antitumor benzophenanthridinium salts.
Journal of Medicinal Chemistry.
1975;
18
708-13
-
22
Fan Y J, Zhou J, Li M.
Effect of nitidine chloride on the life cycle of Ehrlich ascites carcinoma cells in mice.
Acta Pharmacologica Sinica.
1981;
2
46-9
-
23
Wang M H.
Isolation of antitumor alkaloids from Zanthoxylum nitidum and structural study of its alkaloid C.
Chinese Pharmaceutical Bulletin.
1981;
16
48
-
24
Zhu D Y.
Recent advances on the active components in Chinese medicines.
Abstracts of Chinese Medicines (Hong Kong).
1987;
1
251-286
-
25
Kubova N, Smekal E, Kleinwachter V, Cushman M.
Binding properties of nitidine and its indenoisoquinoline analog with DNA.
Studia Biophysica.
1986;
114
251-6
-
26
Gatto B, Sanders M M, Yu C, Wu H Y, Makhey D, LaVoie E J, Liu L F.
Identification of topoisomerase I as the cytotoxic target of the protoberberine alkaloid coralyne.
Cancer Research.
1996;
56
2795-800
-
27
Del Poeta M, Chen S F, Von Hoff D, Dykstra C C, Wani M C, Manikumar G, Heitman J, Wall M E, Perfect J R.
Comparison of in vitro activities of camptothecin and nitidine derivatives against fungal and cancer cells.
Antimicrobial Agents and Chemotherapy.
1999;
43
2862-78
-
28
Wang X, Henningfeld K A, Hecht S M.
DNA topoisomerase I-mediated formation of structurally modified DNA duplexes. Effects of metal ions and topoisomerase I inhibitors.
Biochemistry.
1998;
37
2691-700
-
29
Chen Y Z, Tang G Y, Xu B J, Wu Q J, Lu C Z, Li J Q, Huang Z X.
The formation and crystal structure of dihydronitidine and discussion of anticancer mechanism of nitidine cation.
Science in China Series B.
1992;
35
1101-9
-
30
Larsen A K, Grondard L, Couprie J, Desoize B, Comoe L, Jardillier J C, Riou J F.
The antileukemic alkaloid fagaronine is an inhibitor of DNA topoisomerases I and II.
Biochemical Pharmacology.
1993;
46
1403-12
-
31
Fleury F, Sukhanova A, Ianoul A, Devy J, Kudelina I, Duval O, Alix A J, Jardillier J C, Nabiev I.
Molecular determinants of site-specific inhibition of human DNA topoisomerase I by fagaronine and ethoxidine. Relation to DNA binding.
Journal of Biological Chemistry.
2000;
275
3501-9
-
32
Pezzuto J M, Antosiak S K, Messmer W M, Slaytor M B, Honig G R.
Interaction of the antileukemic alkaloid, 2-hydroxy-3,8,9-trimethoxy-5-methylbenzo[c]phenanthridine (fagaronine), with nucleic acids.
Chemico-Biological Interactions.
1983;
43
323-39
-
33
Herbert J M, Augereau J M, Gleye J, Maffrand J P.
Chelerythrine is a potent and specific inhibitor of protein kinase C.
Biochemical and Biophysical Research Communications.
1990;
172
993-9
-
34
Sampaio-Maia B, Soares-da-Silva P.
Ca2+/calmodulin mediated pathways regulate the uptake of l-DOPA in mouse neuroblastoma neuro 2A cells.
Life Sciences.
2000;
67
3209-20
-
35
Fernandez Y, Ramakrishnan R, Rathinavelu A.
GI-101A breast tumor cell growth.
Life Sciences.
2000;
67
567-75
-
36
Ramakrishnan R, Zell J A, Malave A, Rathinavelu A.
Expression of vascular endothelial growth factor mRNA in GI-101A and HL-60 cell lines.
Biochemical and Biophysical Research Communications.
2000;
270
709-13
-
37
Mueller H, Liu R, David F, Eppenberger U.
Selective modulation of protein kinase A and protein kinase C activities in epidermal growth factor (EGF)-stimulated MCF-7 breast cancer cells.
Biological Chemistry.
1997;
378
1023-9
-
38
Lamm M L, Long D D, Goodwin S M, Lee C.
Transforming growth factor-β1 inhibits membrane association of protein kinase Cα in a human prostate cancer cell line, PC3.
Endocrinology.
1997;
138
4657-64
-
39
Zhu G H, Wong B C, Eggo M C, Yuen S T, Lai K C, Lam S K.
Pharmacological inhibition of protein kinase C activity could induce apoptosis in gastric cancer cells by differential regulation of apoptosis-related genes.
Digestive Diseases and Sciences.
1999;
44
2020-6
-
40
Chmura S J, Dolan M E, Cha A, Mauceri H J, Kufe D W, Weichselbaum R R.
In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chloride induces tumor cell toxicity and growth delay in vivo
.
Clinical Cancer Research.
2000;
6
737-42
-
41
Wolff J, Knipling L.
Antimicrotubule properties of benzophenanthridine alkaloids.
Biochemistry.
1993;
32
13 334-9
-
42
Wang B H, Lu Z X, Polya G M.
Inhibition of eukaryote protein kinases by isoquinoline and oxazine alkaloids.
Planta Medica.
1997;
63
494-8
-
43
Vavreckova C, Gawlik I, Muller K.
Benzophenanthridine alkaloids of Chelidonium majus. II. Potent inhibitory action against the growth of human keratinocytes.
Planta Medica.
1996;
62
491-4
-
44
Ahmad N, Gupta S, Husain M M, Heiskanen K M, Mukhtar H.
Differential antiproliferative and apoptotic response of sanguinarine for cancer cells versus normal cells.
Clinical Cancer Research.
2000;
6
1524-8
-
45
Dai J R, Chai H, Pezzuto J M, Kinghorn A D, Tsauri S, Padmawinata K.
Studies on Indonesian Plants. V. Cytotoxic constituents of the roots of the Indonesian medicinal plant Fibraurea chloroleuca
.
Phytotherapy Research.
1993;
7
290-4
-
46
Chen K T, Hao D M, Liu Z X, Chen Y C, You Z S.
Effect of berberine alone or in combination with argon ion laser treatment on the 9L rat glioma cell line.
Chinese Medicinal Journal (Engl).
1994;
107
808-12
-
47
Iizuka N, Miyamoto K, Okita K, Tangoku A, Hayashi H, Yosino S, Abe T, Morioka T, Hazama S, Oka M.
Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines.
Cancer Letters.
2000;
148
19-25
-
48
Chi C W, Chang Y F, Chao T W, Chiang S H, Peng F K, Lui W Y, Liu T Y.
Flow-cytometric analysis of the effect of berberine on the expression of glucocorticoid receptors in human hepatoma HepG2 cells.
Life Sciences.
1994;
54
2099-2107
-
49
Lin H L, Chang Y F, Liu T Y, Wu C W, Chi C W.
Submicromolar paclitaxel induces apoptosis in human gastric cancer cells at early G1 phase.
Anticancer Research.
1998;
18
3443-9
-
50
Yang I W, Chou C C, Yung B Y.
Dose-dependent effects of berberine on cell cycle pause and apoptosis in Balb/c 3T3 cells.
Naunyn-Schmiedebergs Archives of Pharmacology.
1996;
354
102-8
-
51
Chang K S, Gao C, Wang L C.
Berberine-induced morphologic differentiation and down-regulation of c-Ki-ras2 protooncogene expression in human teratocarcinoma cells.
Cancer Letters.
1990;
55
103-8
-
52
Miura N, Yamamoto M, Ueki T, Kitani T, Fukuda K, Komatsu Y.
Inhibition of thymocyte apoptosis by berberine.
Biochemical Pharmacology.
1997;
53
1315-22
-
53
Kuo C L, Chou C C, Yung B Y.
Berberine complexes with DNA in the berberine-induced apoptosis in human leukemic HL-60 cells.
Cancer Letters.
1995;
93
193-200
-
54
Ren J, Chaires J B.
Sequence and structural selectivity of nucleic acid binding ligands.
Biochemistry.
1999;
38
16 067-75
-
55
Lee S J, Kim J B, Lee S W, Kim J H.
Enhanced cytotoxicity of berberine and some anticancer nucleotides against tumor cell-lines.
Archives of Pharmacal Research.
1995;
18
138-9
-
56
Zhang R X, Dougherty D V, Rosenblum M L.
Laboratory studies of berberine used alone and in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea to treat malignant brain tumors.
Chinese Medicinal Journal (English Edition).
1990;
103
658-65
-
57
Lin H L, Liu T Y, Wu C W, Chi C W.
Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel.
British Journal of Cancer.
1999;
81
416-22
-
58
Lin H L, Liu T Y, Lui W Y, Chi C W.
Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells.
Cancer.
1999;
85
1937-42
-
59
Dai J R, Chai H, Pezzuto J M, Kinghorn A D, Tsauri S, Padmawinata K.
Studies on Indonesian Plants. V. Cytotoxic constituents of the roots of the Indonesian medicinal plant Fibraurea chloroleuca
.
Phytotherapy Research.
1993;
7
290-4
-
60
Makhey D, Gatto B, Yu C, Liu A, Liu L F, LaVoie E J.
Protoberberine alkaloids and related compounds as dual inhibitors of mammalian topoisomerase I and II.
Medicinal Chemistry Research.
1995;
5
1-12
-
61
Kobayashi Y, Yamashita Y, Fuji N, Takaboshi K, Kawakami T, Kawamura M, Mizukami T, Nakano H.
Inhibitors of DNA topoisomerase I and II isolated from the Coptis rhizomes
.
Planta Medica.
1995;
61
414-8
-
62
Kim S A, Kwon Y, Kim J H, Muller M T, Chung I K.
Induction of topoisomerase II-mediated DNA cleavage by a protoberberine alkaloid, berberrubine.
Biochemistry.
1998;
37
16 316-24
-
63
Xia G C, Zang J Y, Lu X M, Xiao P G.
Resource utilization and herbal study of ”malinzi” (Iris lactea Pall. var. chinensis).
Acta Pharmacentica Sinica.
1985;
20
316-9
-
64
Li D H, Hao X G, Zhang S K, Wang S X, Liu R Y, Ma K S, Yu S P, Jiang H, Guan J F.
Antitumor effect and toxicity of irisquinone.
Acta Pharmacologica Sinica.
1981;
2
131-4
-
65
Wang S X, Liu M F, Yuan L, Zhang W L, Li D H.
Effects of irisquinone on cyclic nucleotides in plasma, cancer and other tissues of mice bearing U14 tumor.
Chinese Journal of Clinical Oncology.
1986;
13
241-3
-
66
Li W M, Wang S H, Kuang P, Qu B X, Song H L, Zhu L X.
Radiosensitizing effect of an active principle Iq7611 from the seed of Iris lactea var. chinenesis
.
Tumor.
1987;
7
97-9
-
67
Chitra M, Sukumar E, Suja V, Devi C S.
Antitumor, anti-inflammatory and analgesic property of embelin, a plant product.
Chemotherapy.
1994;
40
109-113
-
68
Chitra M, Sukumar E, Devi C S.
[3
H]-Thymidine uptake and lipid peroxidation by tumor cells on embelin treatment: an in vitro study.
Oncology.
1995;
52
66-8
-
69
Yuan K, Hu R, Ji C, Yin M.
New method for preparing oridonin by column chromatography.
China Journal of Chinese Materia Medica.
1997;
22
478-80, 511
-
70
Wang R L, Gao B L, Xiong M L, Mei Q D, Fan K S, Zuo Z K, Lang T L, Gao G Q, Ji Z C, Wei D C.
Potentiation by Rabdosia rubescens on chemotherapy of advanced esophageal carcinoma.
Chinese Journal of Oncology.
1986;
8
297-9
-
71
Wang R L.
A report of 40 cases of esophageal carcinoma surviving for more than 5 years after treatment with drugs.
Chinese Journal of Oncology.
1993;
15
300-2
-
72
Porterfield H.
UsToo PC-SPES surveys: review of studies and update of previous survey results.
Molecular Urology.
2000;
4
289-91
-
73
de la Taille A, Hayek O R, Burchardt M, Burchardt T, Katz A E.
Role of herbal compounds (PC-SPES) in hormone-refractory prostate cancer: two case reports.
Journal of Alternative and Complementary Medicine.
2000;
6
449-51
-
74
Lou F C, Ding L S, Ma Q Y, Du F L.
Natural antineoplastic compounds and their structure-activity relationships.
Journal of Nanjing College of Pharmacy.
1986;
17
152-9
-
75
Fujita T, Takeda Y, Sun H D, Minami Y, Marunaka T, Takeda S, Yamada Y, Togo T.
Cytotoxic and antitumor activities of Rabdosia diterpenoids.
Planta Medica.
1988;
54
414-7
-
76
Wang M Y, Lin C, Zhang T M.
Cytokinetic effects of oridonin on leukemia L1210 cells.
Acta Pharmacologica Sinica.
1985;
6
195-8
-
77
Li X T, Lin C, Li P Y.
Comparison of in vitro assays for the cytotoxic effect of anticancer drugs.
Chinese Journal of Oncology.
1986;
8
184-6
-
78
Yu J J, Reed E.
Preliminary study of the effect of selected Chinese natural drugs on human ovarian cancer cells.
Oncology Reporter.
1995;
2
571-5
-
79
Wang M Y, Lin C, Zhang T M.
Autoradiographic study on the effects of oridonin on DNA, RNA and protein synthesis of leukemia L 1210 cells.
Acta Pharmacologica Sinica.
1987;
8
164-5
-
80
Li Y, Zhang T M.
Effect of oridonin on cell-free DNA synthesis in vitro
.
Acta Pharmacologica Sinica.
1988;
9
465-7
-
81
Gao Z G, Ye Q X, Zhang T M.
Synergistic effect of oridonin and cisplatin on cytotoxicity and DNA cross-link against mouse sarcoma S180 cells in culture.
Acta Pharmacologica Sinica.
1993;
14
561-4
-
82
Zhang T M, Shou M G, Wang M Y.
Antitumor effects of different combinations of oridonin, bleomycin A5 and nitrocaphane.
Acta Pharmacologica Sinica.
1986;
7
457-60
-
83
Jiang B, Lu Z Q, Hou A J, Zhao Q S, Sun H D.
ent-Kaurane diterpenoids from Isodon lungshengensis
.
Journal of Natural Products.
1999;
62
941-5
-
84
Sun H D, Lin Z W, Niu F D, Lin L Z, Chai H B, Pezzuto J M, Cordell G A.
Cytotoxic ent-kaurene diterpenoids from three Isodon species.
Phytochemistry.
1995;
38
437-42
-
85
Fujita E, Nagao y, Node M, Kaneko K, Nakazawa S, Kuroda H.
Antitumor activity of the Isodon diterpenoids; structural requirements for the activity.
Experientia.
1976;
32
203-6
-
86
Zhai J K, Han W C, Ju X H.
Crystal structure of nervosin and the electronic structure of its anticancer-active zone.
Acta Chimica Sinica.
1993;
51
854-9
-
87
Fujita E, Nagao Y, Kaneko K, Nakazawa S, Kuroda H.
The antitumor and antibacterial activity of the Isodon diterpenoids.
Chemical and Pharmaceutical Bulletin (Tokyo).
1976;
24
2118-27
-
88
Hall I H, Lee K H, Okano M, Sims D, Ibuka T, Liou Y F, Imakura Y.
Antitumor agents. XLII. Comparison of antileukemic activity of helenalin, brusatol and bruceantin and their esters on different strains of P388 lymphocytic leukemic cells.
Journal of Pharmaceutical Sciences.
1981;
70
1147-50
-
89
Liao L L, Kupchan S M, Horwith S B.
Mode of action of the antitumor compound bruceantin, an inhibitor of protein synthesis.
Molecular Pharmacology.
1976;
12
167-76
-
90
Garnick M B, Blum R H, Canellos G P, Mayer R J, Parker L, Skarin A T, Li F P, Henderson I C, Frei E.
Phase I trial of bruceantin.
Cancer Treatment Reports.
1979;
63
1929-32
-
91
Amato D A, Borden E C, Shiraki M, Enterline H AT, Rosenbaum C, Davis H L, Paul A R, Stevens C M, Lerner H J.
Evaluation of bleomycin, chlorozotocin, MGBG, and bruceantin in patients with advanced soft tissue sarcoma, bone sarcoma, or mesothelioma.
Investigational New Drugs.
1985;
3
397-401
-
92
Wiseman C L, Yap H Y, Bedikian A Y, Bodey G P, Blumenschein G R.
Phase II trial of bruceantin in metastatic breast carcinoma.
American Journal of Clinical Oncology.
1982;
5
389-91
-
93
Cheng J H, Long H, Zu J L.
Therapeutic analysis of treatment of recurrent metastatic gastrointestinal carcinomas in 35 patients with Brucea javanica emulsion ”Yandanziyou”.
Chinese Traditional Patent Medicine.
1991;
13
21-2
-
94
Wang Z Q.
Combined therapy of brain metastasis in lung cancer.
Chinese Journal of Integrated Traditional and Western Medicine.
1992;
12
609-10
-
95
Lu J B, Shu S Y, Cai J Q.
Experimental study on effect of Brucea javanica oil emulsion on rabbit intracranial pressure.
Chinese Journal of Integrated Traditional and Western Medicine.
1994;
14
610-11
-
96
Wang J Z, Chen D Y, Su Y Y.
Analytical study on processing of Scutellaria baicalensis Georgi by HPLC.
China Journal of Chinese Materia Medica.
1994;
19
340-1
-
97
Tomimori T, Miyaichi Y, Kizu H.
On the flavonoid constituents from the roots of Scutellaria baicalensis Georgi. I.
Yakugaku Zasshi.
1982;
102
388-91
-
98
Motoo Y, Sawabu N.
Antitumor effects of saikosaponins, baicalin and baicalein on human hepatoma cell lines.
Cancer Letters.
1994;
86
91-5
-
99
Ikemoto S, Sugimura K, Yoshida N, Yasumoto R, Wada S, Yamamoto K, Kishimoto T.
Antitumor effects of scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines.
Urology.
2000;
55
951-5
-
100 Niederberger E, Meiers S, Genzlinger A, Zankl H, Tang W C, Eisenbrand G, Marko D. Flavones and inhibition of tumor cell growth: new aspects on the mechanism of action. In: Eisenbrand G, Dayan AD, Elias PS, Grunow W, Schlatter J, editors Carcinogenic and anticarcinogenic factors in food. Wiley-VCH Weinheim; 1998: 512-3
-
101
Matsuzaki Y, Kurokawa N, Terai S, Matsumura Y, Kobayashi N, Okita K.
Cell death induced by baicalein in human hepatocellular carcinoma cell lines.
Japanese Journal of Cancer Research.
1996;
87
170-7
-
102
Austin C A, Patel S, Ono K, Nakane H, Fisher L M.
Site-specific DNA cleavage by mammalian DNA topoisomerase II induced by novel flavone and catechin derivatives.
Biochemical Journal.
1992;
282
883-9
-
103
Chan F L, Choi H L, Chen Z Y, Chan P S, Huang Y.
Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin.
Cancer Letters.
2000;
160
219-28
-
104
Huang H C, Hsieh L M, Chen H W, Lin Y S, Chen J S.
Effects of baicalein and esculetin on transduction signals and growth factors expression in T-lymphoid leukemia cells.
European Journal of Pharmacology.
1994;
268
73-8
-
105
So F V, Guthrie N, Chambers A F, Moussa M, Carroll K K.
Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and Citrus juices.
Nutrition and Cancer.
1996;
26
167-81
-
106
So F V, Guthrie N, Chambers A F, Carroll K K.
Inhibition of proliferation of estrogen receptor-positive MCF-7 human breast cancer cells by flavonoids in the presence and absence of excess estrogen.
Cancer Letters.
1997;
112
127-33
-
107
Chang W S, Lee Y J, Lu F J, Chiang H C.
Inhibitory effects of flavonoids on xanthine oxidase.
Anticancer Research.
1993;
13
2165-70
-
108
Umezawa K.
Inhibition of experimental metastasis by enzyme inhibitors from microorganisms and plants.
Advances in Enzyme Regulation.
1996;
36
267-81
-
109
Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M.
Antiproliferative activity of flavonoids on several cancer cell lines.
Bioscience, Biotechnology and Biochemistry.
1999;
63
896-9
-
110
Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M.
Effect of Citrus flavonoids on HL-60 cell differentiation.
Anticancer Research.
1999;
19(A)
1261-9
-
111
Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M.
HL-60 differentiating activity and flavonoid content of the readily extractable fraction prepared from Citrus juices.
Journal of Agricultural and Food Chemistry.
1999;
47
128-35
-
112
Bracke M, Vyncke B, Opdenakker G, Foidart J M, De Pestel G, Mareel M.
Effect of catechins and citrus flavonoids on invasion in vitro
.
Clinical and Experimental Metastasis.
1991;
9
13-25
-
113
Takanaga H, Ohnishi A, Yamada S, Matsuo H, Morimoto S, Shoyama Y, Ohtani H, Sawada Y.
Polymethoxylated flavones in orange juice are inhibitors of P-glycoprotein but not cytochrome P450 3A4.
Journal of Pharmacology and Experimental Therapeutics.
2000;
293
230-6
-
114
Ikegawa T, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Naito M, Tsuruo T, Ohtani H, Sawada Y.
Inhibition of P-glycoprotein by orange juice components, polymethoxyflavones in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells.
Cancer Letters.
2000;
160
21-8
-
115
Institute of H aematology, Chinese Academy of Medical S ciences.
Clinical studies of Dang Gui Lu Hui Wan in the treatment of CML.
Chinese Journal of Internal Medicine.
1979;
15
86-8
-
116
Wu L M, Yang Y P, Zhu Z H.
Studies on the active principles of Indigofera tinctoriain the treatment of CML.
Comm Chinese Herb Med.
1979;
9
6-8
-
117
Ji X J, Zhang F R, Lei J L, Xu Y T.
Studies on the antineoplastic effect and toxicity of synthetic indirubin.
Acta Pharmacentica Sinica.
1981;
16
146-8
-
118
Indirubin cooperative g roup.
Clinical study of indirubin in the treatment of 314 patients with chronic granulocytic leukemia.
Chinese Journal of Hematology.
1980;
1
132
-
119
Gan W J, Yang T Y, Wen S D, Liu Y Y, Tan Z, Deng C A, Wu J X, Liu M P.
Studies on the mechanism of indirubin action in treatment of chronic myelocytic leukemia (CML). II. 5′-Nucleotidase in the peripheral white blood cells of CML.
Chinese Journal of Hematology.
1985;
6
611-3
-
120
Qian L S, Xue Y P, Zhang X M, Yang T Y, Yan W W, Wang Z C.
Observation on the long period effect of indirubin in the treatment of 57 cases of chronic myelogenous leukemia.
Chinese Journal of Hematology.
1991;
12
125-7
-
121
Zhang L, Wu G Y, Qiu C C.
Effect of indirubin on DNA synthesis in vitro
.
Acta Academiae Medicinae Sinicae.
1985;
7
112-6
-
122
Gan W J, Yang T Y, Wang Z C, Qian L S, Ma J, Ge Y Q, Cheng B J, Li Z M, Bo H Q.
Studies on the antitumor mechanism of indirubin by treatment of chronic myelocytic leukemia (CML).
Chinese Biochemical Journal.
1987;
3
225-30
-
123
Du D J, Ceng Q T.
Effect of indirubin on the incorporation of isotope labeled precursors into nucleic acid and protein of tumor tissues.
Chinese Traditional and Herbal Drugs.
1981;
12
406-9
-
124
Du D G, Ceng Q T, Wen Z S, Wan X P.
Study on the incorporation of 3H-TdR into DNA of liver and spleen of L7212, a lymphatic leukemia in mice.
Chinese Journal of Hematology.
1982;
3
277-80
-
125
Wu G Y, Liu J Z, Fang F D, Zuo J.
Studies on the mechanism of indirubin action in the treatment of chronic granulocytic leukemia. V. Binding between indirubin and DNA and identification of the type of binding.
Scientia Sinica.
1982;
25B
1071-9
-
126
Lee K, Shih C Y, Yang T Y, Chen L S, Chao W M, Sun C S, Wang T C, Pien S K, Sing K H.
Ultratherapeutic effect of indirubin for human chronic granulocytic leukemia.
National Medical Journal of China.
1979;
59
129-32
-
127
You Y C, Mi J X, Wan J H, Yang T Y, Wang Z C, Qian L S.
Indirubin in the treatment of chronic myelocytic leukemia (CML) estimation of labelling index of bone marrow cells by 3H-TdR.
Chinese Journal of Oncology.
1987;
9
418-20
-
128
Chen K Y, Wang Z F, Li C Y, Li W X.
Study on indirubin and indigo by ESR spectrometry.
Chemical Journal of Chinese Universities.
1989;
10
869-71
-
129
Hoessel R, Leclerc S, Endicott J A, Nobel M E, Lawrie A, Tunnah P, Leost M, Damiens E, Marie D, Marko D, Niederberger E, Tang W, Eisenbrand G, Meijer L.
Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases.
Nature Cell Biology.
1999;
1
60-7
-
130
Marko D, Schatzle S, Friedel A, Genzlinger A, Zankl H, Meijer L, Eisenbrand G.
Inhibition of cyclin-dependent kinase 1 (CDK1) by indirubin derivatives in human tumour cells.
British Journal of Cancer.
2001;
84
283-9
-
131
Leclerc S, Garnier M, Hoessel R, Marko D, Bibb J A, Snyder G L, Greengard P, Biernat J, Wu Y Z, Mandelkow E M, Eisenbrand G, Meijer L.
Indirubins inhibit glycogen synthase kinase-3β and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer’s disease. A property common to most cyclin-dependent kinase inhibitors?.
Journal of Biological Chemistry.
2001;
276
251-60
-
132
Sielecki T M, Boylan J F, Benfield P A, Trainor G L.
Cyclin-dependent kinase inhibitors: useful targets in cell cycle regulation.
Journal of Medicinal Chemistry.
2000;
43
1-18
-
133
Buolamwini J K.
Cell cycle molecular targets in novel anticancer drug discovery.
Current Pharmaceutical Design.
2000;
6
379-92
-
134
Wang J H, You Y C, Mi J X, Ying H G.
Effect of indirubin on hematopoietic cell production.
Acta Pharmacologica Sinica.
1981;
2
241-4
-
135
Wen Z J, Liu Y, Yi Z P, Yang Y S.
Effects of indirubin on the histology and histochemistry of canine and rat livers.
Bulletin of Chinese Materia Medica.
1988;
13
306-7
-
136
Sichnan Institute of Traditional Chinese M edicine.
Subacute toxicity of indirubin in dogs.
Chinese Traditional and Herbal Drugs.
1981;
12
27-9
-
137
Cai Y Y, Xu C L, Li S H, Liu Y.
Studies on sister chromatid exchanges induced by harringtonine, indirubin and pyquiton before or after activation with microsome enzyme.
Acta Academiae Medicinae Sinicae.
1983;
5
161-4
-
138
Feng B Z, Zhang Y H, Qian L S, Chu Y L.
Effect of indirubin on SCE frequencies of BM cells in chronic myeloid leukemia.
Acta Academiae Medicinae Sinicae.
1984;
6
308-10
-
139
Feng B Z.
Sister chromatid exchange frequency of bone marrow cells and its response to indirubin in chronic myeloid leukemia.
Chinese Journal of Oncology.
1984;
6
357-60
-
140
Wu K M, Zhang M Y, Fang Z, Huang L.
Synthesis of N
1-substituted derivatives of indirubin, an antileukemic compound.
Acta Pharmacentica Sinica.
1984;
19
513-8
-
141
Ji XJ Zhang F R.
Antineoplastic effect of indirubin derivatives and their structure-activity relationship.
Acta Pharmacentica Sinica.
1985;
20
137-9
-
142
Zeng Q T, Du D J, Xie D C, Wang X P, Rau C Q.
Antitumor activities of indirubin derivatives.
Chinese Traditional and Herbal Drugs.
1982;
13
24-30
-
143
Gu Y C, Li G L, Yang Y P, Fu J P, Li C Z.
Synthesis of some halogenated indirubin derivatives.
Acta Pharmacentica Sinica.
1989;
24
629-32
-
144
Zeng Q T, Du D J, Si X F, Ran C Q, Wu X P.
Antitumor activity of 5′-iodoindirubin.
West China Pharm Sci.
1991;
6
63-8
-
145
Wu G Y, Liu J Z, Zhang L.
Effect of bisindole compounds with three different kinds of linkage on the synthesis of nucleic acid and protein.
Progress in Biochemistry and Biophysics.
1985;
61
48-51
-
146
Wu K M, Zhang M Y, Fang Z, Huang L.
Potential antileukemic agents, synthesis of derivatives of indirubin, indigo, and isoindigotin.
Acta Pharmacentica Sinica.
1985;
20
821-6
-
147
Ji X J, Liu X M, Li K, Chen R H, Wang L G.
Pharmacological studies of meisoindigo: absorption and mechanism of action.
Biomedical and Environmental Sciences.
1991;
4
332-7
-
148
Liu X M, Wang L G, Li H Y, Ji X J.
Induction of differentiation and down-regulation of c-myb gene expression in ML-1 human myeloblastic leukemia cells by the clinically effective anti-leukemia agent meisoindigo.
Biochemical Pharmacology.
1996;
51
1545-51
Dr. Barbara Bertram
Toxicology and Cancer Risk Factors
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Germany
Email: b.bertram@dkfz.de
Fax: +49 6221-423031
