Selective Inhibitory Effect of Bufalin on Growth of Human Tumor Cells in vitro: Association with the Induction of Apoptosis in Leukemia HL‐60 Cells

Wiley - Tập 85 Số 6 - Trang 645-651 - 1994
Yongkui Jing1, Hidekazu Ohizumi2, Nobuko Kawazoe2, Sachiko Hashimoto2, Yutaka Masuda2, Shigeo Nakajo2, Takemi Yoshida3, Yukio Kuroiwa4, Kazuyasu Nakaya2
1Department of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo.
2Departments of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, 1‐5‐8 Hatanodai, Shinagawa‐ku, Tokyo 142
3Departments of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142
4Departments of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1‐5‐8 Hatanodai, Shinagawa‐ku, Tokyo 142

Tóm tắt

We found that bufalin, an active principle of the Chinese medicine chan'su, has selective inhibitory effects on the growth of various human cancer cells. In order to examine whether the growth‐inhibitory effect of bufalin on human cancer cells is associated with apoptosis, human leukemia cells were treated with bufalin. HL‐60, ML1, and U937 leukemia cells treated with bufalin at 10−8M and above had condensed and fragmented nuclei. Flow cytometric analysis of these cells treated with bufalin showed fragmented DNA smaller than that of the G1 phase. DNA of HL‐60 cells treated with bufalin showed a ladder pattern characteristic of apoptosis, as analyzed by agarose gel electrophoretic analysis. DNA synthesis and topoisomerase II activity of HL‐60 cells were markedly inhibited as the concentration of bufalin was increased. The concentration needed for inducing apoptosis of HL‐60 cells was 10−8M, which is comparable to that of camptothecin, but lower than those of other antitumor drugs such as cisplatin, VP16 and all‐trans retinoic acid. Apoptosis was not observed when human mononuclear and polymorphonuclear cells were treated with 10−6M bufalin for 24 h. These results indicate the association of the growth‐inhibitory effect of bufalin with the induction of apoptosis, at least in HL‐60 cells, and suggest the usefulness of bufalin for differentiation‐apoptosis‐inducing therapy for cancer.

Từ khóa


Tài liệu tham khảo

10.1016/0006-291X(90)91925-I

10.1111/j.1349-7006.1991.tb01827.x

10.1016/0006-291X(91)90162-Z

Zhang L., 1992, Induction by bufalin of differentiation of human leukemia cells HL‐60, U937 and ML1 toward macrophage/monocyte‐like cells and its potent synergistic effect on the differ entiation of human leukemia cells in combination with other inducers, Cancer Res., 52, 4634

10.1006/bbrc.1993.1298

Jing Y., 1993, Differentiation of promyelocytic leukemia cells HL‐60 induced by daidzein in vitro and in vivo, Anticancer Res., 13, 1049

Kaufmann S. H., 1989, Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: a cautionary note, Cancer Res., 49, 5870

10.1016/0167-4889(93)90017-J

10.1111/j.1349-7006.1993.tb00177.x

10.1006/excr.1993.1206

10.1016/0006-2952(90)90733-2

Evans D. L., 1993, Effects of cisplatin on the induction of apoptosis in proliferating hepatoma cells and nonproliferating immature thymocytes, Cancer Res., 53, 2133

10.1111/j.1365-2249.1990.tb08110.x

Unten S., 1989, Stimulation of granulocytic cell iodination by pine cone antitumor substances, J. Leuk. Biol., 45, 166, 10.1002/jlb.45.2.168

Carmichael J., 1987, Evaluation of a tetrazolium‐based semiautomated colorimetric assay: assessment of chemosensitivity testing, Cancer Res., 47, 936

10.1177/26.9.361885

10.4049/jimmunol.145.6.1859

10.1016/0014-4827(85)90426-4

10.1016/0006-291X(92)90438-Q

10.1006/bbrc.1993.1584

Aller P., 1992, Camptothecin induces differ entiation and stimulates the expression of differentiation‐related genes in U937 human promyelocytic leukemia cells, Cancer Res., 52, 1245

Solary E., 1993, Differentiation induction of apoptosis in undifferentiated and differentiated HL‐60 cells by topoisomerase I and II inhibitors, Blood, 81, 1359, 10.1182/blood.V81.5.1359.1359

Thông tin
Thông tin xuất bản

Wiley

Tập 85 Số 6

645-651

Thông tin tác giả