Interaction of a standardized mistletoe (Viscum album) preparation with antitumor effects of Trastuzumab in vitro

Abstract

BackgroundBesides conventional anticancer therapy many breast cancer patients use complementary and alternative medicine (CAM) like the medicinal herb mistletoe (Viscum album L.). To gain more knowledge about possible herb-drug interactions between CAM and conventional anticancer medications, in the present in vitro study we investigated the effect of a standardized mistletoe preparation on the action of Trastuzumab, a drug used for the treatment of Her-2 positive breast cancer.MethodsThe Her-2 positive human breast carcinoma cell line SK-BR-3 was treated with Trastuzumab. Different doses of the drug were combined with Viscum album extract (VAE) in clinically relevant doses. Proliferation, apoptosis, cell cycle and the secretion of vascular endothelial growth factor (VEGF) were analyzed.ResultsNo inhibition of antitumor efficacy of Trastuzumab by VAE was detected. VAE and Trastuzumab, either alone or in combination, inhibited proliferation of SK-BR-3 cells in vitro. At higher concentrations VAE induced apoptosis, which was not observed for Trastuzumab. Cells treated with Trastuzumab underwent a G0/G1 cell cycle arrest and cells treated with VAE a G2/M arrest. After application of the two drugs in combination both G0/G1 and G2/M arrest was observed. VEGF secretion of SK-BR-3 cells was significantly inhibited by sole treatment with Trastuzumab or VAE. Combined treatment of Trastuzumab and VAE at clinically relevant doses showed additive inhibitory effects on VEGF secretion.ConclusionsVAE did not interfere with cytostatic effects of Trastuzumab on SK-BR-3 cells in vitro. Our in vitro results suggest that no risk of safety by herb drug interactions has to be expected from the exposition of cancer cells to Trastuzumab and VAE simultaneously. In contrast, VAE and Trastuzumab seem to exhibit complementary anti-cancer effects in vitro.

Clinical safety of combined therapy of immune checkpoint inhibitors and Viscum album L. therapy in patients with advanced or metastatic cancer

“…A meta-analysis of clinical studies that applied VA Iscador preparations concluded that it might have beneficial effects in psychosomatic self-regulation in addition to short-term quality of life-improving effects in cancer patients [34]. The experimentally assessed mode of action of VA comprises induction of apoptosis, inhibition of cell proliferation and angiogenesis of the tumour cells as well as anti-inflammatory and immunomodulatory effects [35][36][37][38]. Thus, the immunomodulatory nature of VA raises the question of whether there are immunologic interactions between VA and inhibitors of the PD-1/PDL-1 or CTLA-4 pathways that might lead to increased toxicity for cancer patients.…”

Die Misteltherapie in der Behandlung von Patienten mit einer Krebserkrankung

“…Die Ergebnisse einiger weniger hierzu bisher durchgeführter Untersuchungen weisen darauf hin, dass Mistelextrakte kein oder nur ein geringes Risiko für klinische Interaktionen aufweisen. Es handelt sich dabei vorwiegend um präklinische Studien [40][41][42][43][44][45][46]. Eine erste Phase-I-Studie zeigte für ein Mistelpräparat am Patienten, dass die Pharmakokinetik des Zytostatikums Gemcitabin bei paralleler Anwendung von hohen Dosierungen bis zu 250 mg Mistelextrakt nicht beeinflusst wurde [47].…”

Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer: study protocol for a multi-centre, parallel group, double-blind, randomised controlled clinical trial (MISTRAL)

“…However, in rare cases, a generalised allergic reaction may occur [23,24,47,48]. Unwanted and/or clinically significant interactions with ME and established chemotherapeutic drugs have not been observed [23,40,[49][50][51][52].…”