Apoptosis of Human Highly Metastatic Lung Cancer Cell Line 95-D Induced by Acutiaporberine, a Novel Bisalkaloid Derived from Thalictrum acutifolium

Abstract

The present study demonstrates for the first time that acutiaporberine, a bisalkaloid isolated from the tranditional Chinese medical herb Thalictrum acutifolium (Hand.-Mazz.) Boivin. (TAB), induces apoptosis of a cultured highly metastatic human lung cancer cell line 95-D. Immunohistochemistry assay (IHC) and Western-blot analysis show down-regulation of bcl-2 gene and up-regulation of bax gene and c-myc gene in the treated cells. These results suggest that acutiaporberine may be a natural potential apoptosis-inducing agent for highly metastatic lung cancer.

Abbreviations

TAB:Thalictrum acutifolium (Hand.-Mazz.) Boivin

FCM:flow cytometry

IHC:immunohistochemistry

TCM:traditional Chinese medicine

NCI:the National Cancer Institute of USA

DMSO:dimethyl sulphoxide

FBS:fetal bovine serum

PBS:phosphate buffered saline

PI:propidium iodide

EDTA:ethylenediaminetetraacetic acid disodium salt

UV:ultraviolet

DAB:diaminobenzidine

HRP:horseradish peroxidase streptavidin

References

• 1 Zhang G Q, Ren R G, Kong Q Y, Li Y J, Guan W M. Effects of radix Salivae miltiorrhizae on proliferation, apoptosis and c-myc protein expression of fibroblast in culture of kidney with lupus nephritis.  Chinese J. Integrated Traditional and Western Med. 1997;  17 473-5
• 2 Dong Y, Yang M M, Kwan C Y. In vitro inhibition of proliferation of HL-60 cells by tetrandrine and Coriolus versicolor peptide derived from Chinese medicinal herbs.  Life Sci.. 1997;  60 135-40
• 3 Zhang X, Yang X P, Pan Q C. Studies on the anticancer effect and apoptosis induction in human liver cancer cell line (BEL-7402) by sodium artesunate.  Chinese J. of Herbal Drugs. 1998;  29 467-9
• 4 Tanizawa A, Fujimori A, Fujimori Y, Pommier Y. Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials.  J. Natl. Cancer Inst. 1994;  86 836-42
• 5 Ma J, Peng W L, Liang D, Fu N Y, Pang D B, Xu A L. The extract of Glycyrrhiza uralensis Fisch induces apoptosis in MGC-803 cells and its molecular mechanisms.  Biomedical Res. 2000;  21 129-37
• 6 Todorov D, Damyanova M. Investigations into the acute toxicity of the antitumor alkaloid thaliblastine.  C. R. Acad. Bulg. Sci.. 1975;  28 709-11
• 7 Deliconstantinos G, Ramantanis G, Todorov D. Interaction of 99m Tc-labeled liposomes with Walker tumor cells in vitro. Liposome-mediated introduction of thaliblastione into resistant Walker tumor cells.  Gen. Pharmacol.. 1983;  14 407-11
• 8 Todorov D, Zeller W J. Antiproliferative activity of the non-myelotoxic antitumour agent of plant origin, thaliblastine, on two human glioma cell lines.  J. Cancer. Res. Clin. Oncol.. 1992;  118 83-6
• 9 Lin L Z, Hu S F, Zaw K, Angerhofer C K, Chai H, Pezzuto J M. et al . Thalifaberidine, a cytotoxic aporphine-benzylisoquinoline alkaloid from Thalictrum faberi .  J. Nat. Prod.. 1994;  10 1430-6
• 10 Mircheva J, Stoychkov J. Effect of thaliblastine on transplantable tumors in mice.  Biomed. Exp.. 1976;  25 280-1
• 11 Ilarionova M, Maneva K, Todorov D. Pathomorphological studies on animals bearing experimental tumors treated with thaliblastine.  C. R. Acad. Bulg. Sci.. 1980;  33 719-22
• 12 Lin C W, Su J Y, Zeng L M, Xu A L, Pen W L. Structure determination of a novel ether-linkaged bisalkaloid acutiaporberine.  Chem. J. of Chinese Univ.. 2000;  12 1820-3
• 13 Chen Q, Qi S J, Peng W L, Xu A L. Cytotoxic activity of acutiaporberine, a novel bisalkaloid of plant origin, on several human carcinoma cell lines.  Acta Scientiarum Naturalium Universitatis Sunyatseni. 2001;  40 9-12
• 14 Han R. Methods of Apoptosis Study, in: Research and Development of Anticancer Drugs and Experimental Techniques, the Press Union of Peking. Medical Univ. and China Xiehe Medical Univ Beijing, China; 1997: pp. 389-405
• 15 Sambrook J, Fritsch E F, Maniatis T. Detection and Analysis of Expressed Proteins of Cloned Genes. In: Nancy Ford, editor Molecular Cloning, A Laboratory Manual. 2nd edtion Cold Spring Harbor Laboratory Press 1989: pp. 880-97