Cytotoxic activity and absence of tumor growth stimulation of standardized mistletoe extracts in human tumor models in vitro

Cytotoxic activity and absence of tumor growth stimulation of standardized mistletoe extracts in human tumor models in vitro.

Author information

• 
  ¹Oncotest GmbH, Institute for Experimental Oncology, Am Flughafen 12, 79018 Freiburg, Germany.
  

Abstract

Mistletoe extracts are widely used in complementary and alternative cancer therapy in Europe. The extracts possess cytotoxic, as well as immunostimulatory effects. However, some investigators have suggested that low doses of mistletoe extracts could also induce tumor growth. The mistletoe extracts Helixor A, Helixor M and Helixor P were investigated for growth inhibitory and stimulatory effects in a panel of 38 human tumor cell lines in vitro. Mistletoe lectin I (ML-1), adriamycin and interleukin-6 (IL-6) were used as reference compounds. All three mistletoe preparations showed cytotoxic activity [T/C (Test/Control) < 30%]: Helixor P was the most potent, followed by Helixor M and Helixor A with IC50 (50% inhibitory concentration) values of 68.4, 114 and 133 microg/ml, respectively. The IC50 values of ML-1 and adriamycin were 0.026 and 0.069 microg/ml. None of the human tumor cell lines in the panel showed growth stimulation (T/C (Test/Control) > 125%) by the mistletoe extracts or ML-1, apart from two exceptions in the colon carcinoma cell line HCC-2998, in which Helixor M and ML-1 showed a marginal stimulation (TIC 128% and 131%, respectively) at one concentration only. Further investigations into the latter effect of Helixor M and ML-1 in the HCC-2998 line using five different proliferation assays, modified cell culture conditions and the identical production charge of mistletoe extract, as well as a new one, did not confirm the previous observation. It was concluded that the marginal stimulation found in the earlier experiments was a statistical coincidence. Helixor mistletoe preparations and ML-1 have cytotoxic activity and do not stimulate tumor cell proliferation in vitro which is in accordance with previous scientifically based observations on aqueous mistletoe extracts.

Цитотоксическая активность и отсутствие стимуляции роста опухоли стандартизированных омела экстракты в человеческих опухолевых модели in vitro.

Омела экстракты широко используются в комплементарной и альтернативной рак терапии в Европе. Экстракты обладают цитотоксические, а также иммуностимулирующее действие. Однако, некоторые исследователи предположили, что в низких дозах омела экстракты также может вызвать рост опухоли. В омела экстракты Helixor, Helixor м и Helixor P исследованы для роста тормозящих и стимулирующий эффекты в панели 38 человеческих опухолевых клеточных линий in vitro. Омела лектин я (мл-1), адриамицин и интерлейкина-6 (ил-6) были использованы в качестве исходных соединений. Все три омела препаратов показал, цитотоксическая активность [T/C (тестовый контроль) < 30%]: Helixor P был самым мощным, сопровождаемый Helixor м и Helixor с IC50 (50% ингибирующая концентрация) значения 68.4, 114, 133 микрогр/мл, соответственно. В IC50 значения мл-1 и адриамицин были 0,026 и 0.069 микрогр/мл. Ни одна из человеческих опухолевых клеточных линий в панель показывала стимуляции роста (T/C (тестовый контроль) > 125%) омела экстракты или мл-1, кроме двух исключений в рак толстой кишки клеточной линии ГЦК-2998, в котором Helixor м и мл-1 показали незначительное стимулирование (тИЦ 128% и 131%, соответственно) на одно только концентрация. Дальнейшие исследования в последний эффект Helixor м и мл-1 в ГЦК-2998 строки с помощью пяти различных распространения анализов, модифицированные культуры клеток условиях и в одинаковых производственных заряд омела экстракт, а также новый, не подтверждают предыдущие наблюдения. Был сделан вывод о том, что предельная стимуляции, найденные в более ранних экспериментах была статистической случайностью. Helixor омела подготовка и мл-1 У цитотоксической активности и не стимулируют пролиферацию опухолевых клеток in vitro в соответствии с предыдущими научно обоснованные замечания по водный омела экстракты.

Arzneimittelforschung. 2006 Jun;56(6A):508-15.

Immune modulation using mistletoe (Viscum album L.) extracts Iscador.

Büssing A.

Author information

• 
  Krebsforschung Herdecke, Immunological Laboratory, Bochum, Germany. arndt.buessing@uni-wh.de
  

Abstract

One repeatedly finds that mistletoe (Viscum album L.) extracts show immune-modulating effects. This is also true in many cases in the experimental setting. Many of the experimental trials cannot, however, be transferred to the clinical situation - or only in a limited way. The aim of this work was to pursue the question of the extent to which the function of immune-competent cells can be influenced by mistletoe extracts. To do this, 3 clinical studies were carried out. Results from the first two studies will be presented here. In a prospective observational study with defined inclusion and exclusion criteria, the impact of two different doses of Iscador M (Malus) or Iscador Qu (Quercus) on the function and number of T-lymphocytes from tumor patients was studied. The immunological tests took place monthly during the first six months. Thirty-one patients were included in the slow dose group and 36 patients in the group with swift dose escalation. It was postulated that too swift increase in dosage would lead to stronger local reactions and impairment of the stimulation capacity of T-cells taken ex vivo and incubated for 72 h. The evaluation showed that patients with stronger local reactions at the injection site have an impairment of mitogen-induced stimulation capacity of T-cells. However, patients with stronger local reaction showed a significant decrease of HLA-DR+ T cells as compared to patients In a GCP-conform, controlled bicentric phase II study the aim was to investigate the efficacy of a perioperative intravenous mistletoe extract application on the modulation of operation-induced immune suppression. For this purpose 105 patients with breast cancer were recruited. At the treatment centre the patients received an infusion of 1 mg Iscador M Spezial prior to the start of an operation, in addition to normal medication, while this was not practised at the control centre. The primary trial objective was the oxidative burst in granulocytes taken from patients ex vivo prior to surgery, and 1 and 3 days after. In order to take account of possible differences in the two groups, propensity scores were used as the basis for a matched pair analysis. It became clear that inhibition of the granulocyte function in the treatment group was significantly less marked (p < 0.001; Wilcoxon). Mistletoe extract-related adverse reactions were not observed. Thus this special form of application could minimise the immune suppression triggered by anaesthesia and operation stress.

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