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PubMed1976

Breast cancer and use of rauwolfia and other antihypertensive agents in hypertensive patients: a nationwide case-control study in Finland.

Two nationwide registers, the Finnish Cancer Registry and a register of persons entitled to free drugs for hypertension, were linked in a case-control study of the association of breast cancer and use of rauwolfia. Cases were all hypertensive patients in whom breast cancer was diagnosed in 1973. To test the association specifically with rauwolfia, controls were hypertensive women matched with the cases for age and geographic area and approximately matched for duration of treatment for hypertension. There were 109 case-control pairs. Use of any physician-prescribed drugs during the year prior to diagnosis of breast cancer was ascertained from original prescriptions. In the first set of analyses the patients were classified according to the drug used during most days of the year ("main antihypertensive agent"). In the second set a person qualified as a user of the respective drug regardless of the amount taken. The relative risks in the use of rauwolfia, methyldopa, another synthetic antihypertensive or a diuretic as main antihypertensive agent all ranged between 0.90 and 1.11. The results based on use of a drug in any amount were similar. Next, pairs in which duration of treatment for hypertension was different for cases and controls were excluded. The relative risk associated with use of rauwolfia as main antihypertensive agent then increased from 1.00 to 1.30 and the risk associated with use of any amount of rauwolfia from 1.16 to 2.14. Simultaneously, the relative risk in the use of digitalis was raised from 1.33 to 2.67 and of nitroglycerin from 1.00 to 1.71. Cases also used more types of antihypertensive agents simultaneously than controls. There was no association between rauwolfia-use and breast cancer in analyses limited to pairs in which neither case nor control used digitalis. Thus, there was not a consistent drug-specific association between rauwolfia-use and breast cancer in hypertensive patients. An underlying association of hypertension, heart disease or its treatment (digitalis) and breast cancer may have confounded some of the results of this and earlier studies. In conclusion, it is unlikely that use of rauwolfia increases the risk of breast cancer.

Adult↗
PubMed2002

Augmentation of immune cell activity against tumor cells by Rauwolfia radix.

In this study, we investigated the effect of Rauwolfia radix on heat shock protein (HSP) 70 expression and cytotoxicity against tumor cells in activated human T cells. When activated T cells were cultured with Rauwolfia radix for 18 h, HSP70 expression after heat shock was remarkably increased, and cytotoxicity against T98G tumor cells was augmented. Moreover, Rauwolfia radix also enhanced the cytotoxicity of heat shocked activated T cells against Molt-4 and T98G tumor cells. Secretions of interferon-gamma (IFN-gamma) and tumor necrosis alpha (TNF-alpha), due to Concanavalin A (Con A) stimulation, were increased by Rauwolfia radix in activated T cells. To investigate the antitumor effect in vivo, EL-4 tumor-bearing mice were administered with Rauwolfia radix in drinking water. The survival period of the Rauwolfia radix treatment group was significantly prolonged compared with that of the control group. Reserpine, the major active ingredient of Rauwolfia radix, also enhanced the cytotoxicity of activated T cells against Molt-4 and T98G tumor cells, and prolonged the survival period of EL-4 tumor-bearing mice. Taken together, our results suggest that Rauwolfia radix can enhance the activity of immune cells against tumor cells.

Animals↗
PubMed2006

Anti-prostate cancer activity of a beta-carboline alkaloid enriched extract from Rauwolfia vomitoria.

The tropical shrub, Rauwolfia vomitoria, is a medicinal plant used traditionally to treat a variety of ailments. A bioactive beta-carboline alkaloid, alstonine, present in this extract was previously shown to have anti-cancer activity against cancer cell lines. This study considers the potential anti-prostate cancer activity of this extract in vitro and in vivo. Rauwolfia vomitoria extract standardized for beta-carboline alkaloids was tested for ability to influence the growth and survival of the human LNCaP prostate cancer cell line. A WST-1 assay was used to measure cell growth, and cell cycle analyses were conducted with flow cytometry. Western blot detection of PARP cleavage and accumulation of cells containing sub-genomic DNA indicated induction of apoptosis. Pathway specific microarray analyses were utilized to identify the effect of Rauwolfia extract on the expression of 225 genes. Mice xenografted with LNCaP cells were treated with the extract or placebo control, and tumor growth was measured for 5 weeks. The effects of the extract on xenografted tumor cell proliferation and apoptosis were measured by in situ BrdU incorporation and TUNEL staining. Rauwolfia extract decreased in vitro cell growth in a dose-dependent manner (p<0.001) and induced the accumulation of G1 phase cells. PARP cleavage demonstrated that apoptosis was induced only at the highest concentration tested (500 microg/ml) which was confirmed by detection of cells containing sub-genomic DNA. The expression of genes associated with DNA damage signaling pathway was up-regulated by Rauwolfia treatment, including that of GADD153 and MDG. The expression of a few cell cycle genes (p21, cyclin D1 and E2F1) was also modulated. These alterations were confirmed by RT-PCR. Tumor volumes were decreased by 60%, 70% and 58% in the groups fed the 75, 37.5 or 7.5 mg/kg Rauwolfia, respectively (Kruskal-Wallis test, p<0.001). The Rauwolfia vomitoria extract significantly suppressed the growth and cell cycle progression of LNCaP cells, in vitro and in vivo.

Alkaloids↗
PubMed1986

Rauwolfia use and breast cancer: a case-control study.

Breast cancer risk among 1,362 cases and 1,250 controls participating in a large multicenter screening program was examined in relation to hypertension and the use of rauwolfia derivatives. A previous diagnosis of hypertension, reported by 22% of the cases and 23% of the controls, was not associated with an increased risk of breast cancer [odds ratio (OR) = 0.9]; nor was there any excess risk for long-term hypertensives. In addition, there was no significant increase in risk associated with use of either rauwolfia derivatives (OR = 1.2), thiazide preparations (OR = 1.2), or methyldopa (OR = 1.1). However, there were significant excess risks among long-term users and those with extended intervals since first use of rauwolfia. Rauwolfia users of 10 or more years' duration or those whose initial use occurred greater than or equal to 10 years before diagnosis had risk ratios of 4.5 (95% Cl, 1.2-19.8) and 3.8 (95% Cl, 2.3-11.6), respectively. These results suggest that women exposed to long-term rauwolfia use have an elevated risk of developing breast cancer, although the results fail to support previous observations of a generalized adverse effect.

Aged↗
PubMedDate not supplied

[Ultrastructure of the cell surface of heteromorphic Nostoc muscorum CALU 304 cocultured with Rauwolfia tissue].

The ultrastructure of the heteromorphic cells (HMCs) of the cyanobacterium Nostoc muscorum CALU 304 grown in pure culture, monoculture, and a mixed culture with the Rauwolfia callus tissue was studied. The comparative analysis of the cell surface of HMCs, the frequency of the generation of cell forms with defective cell walls (DCWFs), including protoplasts and spheroplasts, and the peculiarities of the cell surface ultrastructure under different growth conditions showed that, in the early terms of mixed incubation, the callus tissue acts to preserve the existing cyanobacterial DCWFs, but begins to promote their formation in the later incubation terms. DCWFs exhibited an integrity of their protoplasm and were metabolically active. It is suggested that structural alterations in the rigid layer of the cell wall may be due to the activation of the murolytic enzymes of cyanobacteria and the profound rearrangement of their peptidoglycan metabolism caused by the Rauwolfia metabolites diffused through the medium. These metabolites may also interfere with the functioning of the universal cell division protein of bacteria, FtsZ. In general, the Rauwolfia callus tissue promoted the unbalanced growth of the cyanobacterium N. muscorum CALU 304 and favored its viability in the mixed culture. The long-term incubation of the Rauwolfia tissue with the N. muscorum CALU 304 cells led to their transformation to L-forms.

Cell Membrane↗
PubMed1983

Rauwolfia and breast cancer: no relation found in long term users age fifty and over.

It has been suggested that conflicting findings regarding rauwolfia drugs as predisposing factors for breast cancer can be explained by the hypothesis that use for a long duration predisposes to breast cancer occurring after age 50. In a follow-up study of 2077 women who received prescriptions for rauwolfia drugs there was no excess risk for breast cancer diagnosed at age 50 or greater (morbidity ratio = 0.9 compared to 1.0 expected). In comparing 35 patients in this age group with 168 women who received rauwolfia but remained free of breast cancer, there was no excess risk for long (greater than or equal to 5 yr) duration of use (relative risk = 0.9). Thus, the hypothesis could not be confirmed in this study group. It is likely that the excess risk among long-duration rauwolfia users, if present at all, is less than 2-fold.

Aged↗