Dr. Weeks’ Comment: Reversing cancer happens at the cellular level using Corrective Cancer Care™ and anti-inflammatory seeds now scientists in Israel are demonstrating a mechanism of action –VDCA1 – the voltage gated process at the cellular membrane which is disrupted my toxicities related to chronic inflammation at the cellular level.
“… Israeli Researchers Say They Can Reprogram Cancer Cells Back To Their Pre-Cancer State… VDAC1 is a “gatekeeper” of the mitochondria, the powerhouse of the cell, and is the “key to opening and closing the door to mitochondrial metabolism,” says the head of the research team Professor Varda Shoshan-Barmatz of the Department of Life Sciences and the National Institute for Biotechnology in the Negev (NIBN), an independent research institute facilitating pre-clinical studies of biotech research located within BGU. VDAC1 is crucial for supplying the high energy demands that characterize malignant cells, the univeristy said in a statement…” (source)
Neuro Oncol. 2017 Jul 1;19(7):951-964. doi: 10.1093/neuonc/now297.
Arif T1, Krelin Y1, Nakdimon I1, Benharroch D1, Paul A1, Dadon-Klein D1, Shoshan-Barmatz V1.
Abstract
BACKGROUND:
Glioblastoma (GBM), an aggressive brain tumor with frequent relapses and a high mortality, still awaits an effective treatment. Like many cancers, GBM cells acquire oncogenic properties, including metabolic reprogramming, vital for growth. As such, tumor metabolism is an emerging avenue for cancer therapy. One relevant target is the voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein controlling cell energy and metabolic homeostasis.
METHODS:
We used VDAC1-specific short interfering (si)RNA (si-VDAC1) to treat GBM cell lines and subcutaneous or intracranial-orthotopic GBM xenograft mouse models. Tumors were monitored using MRI, immunohistochemistry, immunoblotting, immunofluorescence, quantitative real-time PCR, transcription factor expression, and DNA microarray analyses.
RESULTS:
Silencing VDAC1 expression using si-VDAC1 in 9 glioblastoma-related cell lines, including patient-derived cells, led to marked decreases in VDAC1 levels and cell growth. Using si-VDAC1 in subcutaneous or intracranial-orthotopic GBM models inhibited tumor growth and reversed oncogenic properties, such as reprogrammed metabolism, stemness, angiogenesis, epithelial-mesenchymal transition, and invasiveness. In cells in culture, si-VDAC1 inhibits cancer neurosphere formation and, in tumors, targeted cancer stem cells, leading to their differentiation into neuronal-like cells. These VDAC1depletion-mediated effects involved alterations in transcription factors regulating signaling pathways associated with cancer hallmarks.
CONCLUSION:
VDAC1 offers a target for GBM treatment, allowing for attacks on the interplay between metabolism and oncogenic signaling networks, leading to tumor cell differentiation into neuron- and astrocyte-like cells. Simultaneously attacking all of these processes, VDAC1 depletion overcame GBM heterogeneity and can replace several anticancer drugs that separately target angiogenesis, proliferation, or metabolism.