Effect Of Mistletoe Extract On Growth And Proliferation Of Prostate Cancer Cells.

Abstract Complementary and alternative medicines are explored for their role in improving the quality of life of patients with cancer. Many anti-cancer drugs have been derived from natural sources. Mistletoe extract, composed of lectins, viscotoxins, flavonoids, and other biologically active substances, has two mechanisms of action: tumor cytotoxicity and immunomodulation. The cytotoxic effects of mistletoe extract are a result of protein synthesis interference, cell cycle inhibition, and apoptosis induction. Further, mistletoe extract has been shown to have anti-angiogenic properties. In Europe, Helixor M, mistletoe extract from Viscum album mali, is used as an anthroposophic medicine in the treatment of malignant and non-malignant tumors, malignant disorders with accompanying impairment of the hematopoietic organs, stimulation of bone marrow activity, reducing the risk of tumor recurrence, and diagnosed pre-cancerous disorders. However, only limited evaluation of mistletoe extract has been conducted in the United States. We studied the effects of Helixor M in prostate cancer. To evaluate its effect on cell proliferation and survival, we treated androgen receptor (AR) positive (LNCaP, LAPC4 and VCaP) and AR negative (PC3 and DU-145) cell lines with Helixor M. Our data indicates that LNCaP and LAPC4 cells were most sensitive to Helixor M while PC3, DU-145, and VCaP cells were relatively resistant to treatment. While AR protein levels and NF-kappaB subunits remained unaffected by treatment, there was an induction of apoptosis along with a concomitant decrease in LC3B, an autophagy marker, in all the sensitive prostate cancer cell lines. In search of pathways that may synergize with growth inhibition by Helixor M, we utilized CRISPR knockouts of TBK1, a kinase involved in autophagy induction, in LNCaP cells and tested whether TBK1 knockouts are synthetically lethal with Helixor M. Helixor M induced increased apoptosis in TBK1 knockouts as compared to parental LNCaP cells, indicating that TBK1 loss might be synthetically lethal with Helixor M. Citation Format: Kavya Boyapati, Rajendra Kumar, Lillian Wilson, Yuhan Yang, Deven Topiwala, Keerti Soundappan, Eleni Panagopoulos, Ivelisse Page, Jennifer Durham, Michael Carducci, Channing Paller, Sushant Kachhap. Effect of mistletoe extract on growth and proliferation of prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB102.