A small study from researchers in India has found that a short course of an oral combination of resveratrol and copper was associated with reduced biological markers of aggressiveness in glioblastoma tumors, without reported side effects. Patients who took the nutraceutical before surgery showed lower levels of several key cancer-related markers in their tumor samples, and the approach targets harmful DNA-containing particles released from dying cancer cells.
Professor Indraneel Mittra and colleagues at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), part of the Tata Memorial Centre near Mumbai, tested a novel strategy in patients with glioblastoma, a highly aggressive brain tumor for which median survival remains around 15 months despite standard treatments such as surgery, chemotherapy and radiotherapy.
In the study, published in BJC Reports, ten patients with glioblastoma awaiting surgery were given an oral tablet containing low doses of the nutraceuticals resveratrol and copper (R-Cu) four times a day for an average of 11.6 days before their operation. Another ten patients with similarly aggressive tumors who did not receive R-Cu served as controls, according to the study and a summary released by Cactus Communications.
During surgery, tumor tissue from both groups was collected and analyzed using microscopy, immunostaining, immunofluorescence and transcriptome sequencing. The researchers report that treatment with R-Cu led to marked deactivation of cell-free chromatin particles (cfChPs) in the tumor microenvironment and was accompanied by significant changes in multiple biomarkers of tumor aggressiveness.
According to the BJC Reports paper and associated press materials, average levels of Ki-67, a protein widely used as a marker of how fast glioblastoma cells are dividing, were almost one-third lower in the R-Cu–treated samples compared with untreated controls. Biomarkers associated with nine hallmarks of cancer were present in 57% fewer cells in the treated group. Levels of six immune checkpoint proteins were on average 41% lower, and three stem-cell–related markers were reduced by about 56% in the treated tumors. No toxic side effects attributable to R-Cu were reported during the short pre-surgical course.
“These results suggest that a simple, inexpensive and non-toxic nutraceutical tablet potentially has the power to heal glioblastoma,” Professor Mittra is quoted as saying in material disseminated via ScienceDaily and EurekAlert.
The proposed mechanism centers on neutralizing cfChPs — fragments of DNA and associated proteins released from dying cancer cells that can be taken up by surviving cells and promote DNA damage and inflammation. Earlier work by Mittra’s group suggested that when resveratrol and copper are combined, they generate oxygen radicals capable of deactivating these cfChPs. In the current study, cfChPs were abundant in untreated tumor tissue but were reported to be nearly absent from samples taken from patients who had received the R-Cu tablets.
Professor Mittra explains in the press materials: “The cell-free chromatin particles, fragments of DNA released by dying cancer cells, inflame the surviving cancer cells. This makes the disease more aggressive. If you eliminate the cell-free chromatin, which is what the resveratrol-copper tablets do, the cancer is subdued.”
Transcriptome analyses from the BJC Reports study indicated upregulation of pro-apoptotic genes and downregulation of anti-apoptotic genes in R-Cu–treated tumors, consistent with increased intrinsic apoptosis and more efficient clearance of apoptotic debris. The authors report that this was associated with a reduction in markers linked to tumor grade and aggressiveness.
One of the notable findings highlighted by the researchers is the reduction in immune checkpoint markers after R-Cu treatment. Immune checkpoint inhibition with monoclonal antibodies is a major, but costly and often toxic, area of modern cancer therapy. By comparison, the R-Cu combination uses widely available nutraceutical ingredients in very low doses. Mittra and colleagues suggest that, if confirmed in larger and longer-term trials, this approach might offer a low-cost means of modulating tumor biology and immune checkpoints without the toxicities seen with some systemic anticancer drugs.
Mittra has also argued that oncology’s traditional focus has been on directly killing cancer cells, a strategy pursued since at least classical Greek medicine, and that targeting cfChPs may represent a shift toward promoting tumor "healing" rather than destruction. The authors caution, however, that the present findings are based on a small, non-randomized cohort and short-term treatment, and they state that further studies are needed to determine whether prolonged R-Cu administration can durably alter tumor behavior or improve survival.
The research builds on the long-standing concept that cancer can resemble an unhealing wound, an analogy first articulated by pathologist Dr. Harold Dvorak in 1986, and explores whether manipulating the tumor microenvironment and inflammatory signals through deactivation of cfChPs can make aggressive tumors less malignant over time.
