Comparative studies of the effects of Tabebuia avellanedae bark extract and beta-lapachone on the hematopoietic response of tumour-bearing mice.
The effects of Tabebuia avellanedae (TACE), traditionally prescribed in the treatment of cancer, and the naphtoquinone beta-lapachone (beta-lap) on the growth and differentiation of granulocyte and macrophage progenitor cells (CFU-GM) were studied in Ehrlich ascites tumour-bearing mice. Myelosuppression concomitant with increases in spleen CFU-GM and in serum colony-stimulating activity (CSA) were observed in these animals. Treatment with TACE (30-500 mg/kg) and beta-lap (1-5mg/kg) reversed these effects in a dose-dependent manner. The optimal biologically active doses of 120 mg/kg TACE and 1mg/kg beta-lap prolonged life span of tumour-bearing mice, both producing the same rate of extension in the duration of survival. Toxic manifestations were produced by the higher doses of beta-lap in normal and tumour-bearing mice. In spite of similarities between treatments, TACE concentrations used to treat the animals presented no traces of beta-lap, as measured by TLC and HPLC analyses. Our findings suggest that the antitumour effect of TACE and beta-lap, acting synergistically with other factors, such as specific cytokines, may result from enhanced macrophage activation against tumour cells. In addition, it is clear from our results that hematopoietic disorders produced by tumours are an important pathological condition that must be considered in drug development.
Queiroz
Mary L S
ML
Departamento de Farmacologia and Hemocentro, Faculdade de Ciências Médicas, Universidade, Estadual de Campinas, UNICAMP, CP 6111, CEP 13083-970, Campinas, SP, Brazil.
Valadares
Marize C
MC
Torello
Cristiane O
CO
Ramos
Aline L
AL
Oliveira
Alaíde B
AB
Rocha
Fabíola D
FD
Arruda
Vanessa A
VA
Accorci
Walter R
WR
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003115:Colony-Stimulating Factors / Q000097:blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D038042:Myelopoiesis / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000097:blood*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects; D016019:Survival Analysis; D029663:Tabebuia / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D003115:Colony-Stimulating Factors; D009285:Naphthoquinones; D010936:Plant Extracts; C014638:beta-lapachone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor