R-Cu made from grape extract, resveratrol, and copper, deactivates chromatin particles, reduces toxicity of chemotherapy drugs
Representative photo from iStock This story has been updated
Rather than migrating cancer cells, conventional cancer therapies — chemotherapy, radiotherapy, and surgery — might also contribute to metastatic spread post-treatment, according to a recent study by the Translational Research Laboratory, Tata Memorial Centre (TMC) in Mumbai.
Dying cancer cells generated by cancer treatment release chromatin particles that turn healthy cells into cancerous ones, spreading the disease from the primary site to other parts of the body, the decade-long research led by Professor Indraneel Mittra found. Chromatin particles (cfChPs, or fragments of chromosomes) merge with healthy chromosomes, leading to the formation of new tumors, TMC’s Advanced Centre for Treatment, Research and Education in Cancer’s (ACTREC) study revealed.
“Chemotherapy and radiotherapy are used to kill cancer cells. The therapy-induced dead cancer cells release small chromosomal fragments called cell-free chromatin particles (cfChPs) which get into the bloodstream and are carried to different organs of the body where they can transform the host cells to form new cancers which are called metastases. We were the first to discover that killing cancer cells can release cfChPs which may potentially cause metastasis,” Mittra told Down to Earth (DTE).
Toxicity associated with chemotherapy is a major therapeutic challenge. The researchers further hypothesised that much of the toxicity of chemotherapy might be due to the release of large quantities of cfChPs from dying cells that could trigger an inflammatory response in healthy cells.
“Chemo-toxicity is not primarily caused by chemotherapeutic drugs, but rather by cfChPs that are released from the first cells that die after chemotherapy. The released cfChPs set in motion a cascading effect, increasingly damaging the DNA of healthy host cells, and triggering inflammatory processes in a vicious cycle that perpetuates and prolongs the toxicity of chemotherapy,” Mitra explained in a press statement.
To contain cancer and prevent the toxicity of chemotherapy, the doctors developed a nutraceutical drug, a medicinal product derived from food sources. R-Cu, the combination of grape extract, resveratrol, and copper, deactivates or neutralises cfChPs and reduces the toxicity of chemotherapy drugs simultaneously.
The researchers used mice in Mittra’s laboratory to demonstrate how this plays out. Mice infected with human breast cancer cells were given chemotherapy, radiotherapy, and surgery. Researchers discovered cfChPs and cancer proteins in the mice’s brains increased post-treatment. Subsequently, biopsies of half of the mice showed that receiving nutraceuticals lowered the level of cfChPs.
These findings led to the hypothesis that fChPs may contain cancer-causing genes that can enter the healthy cells of other organs through the bloodstream to cause the metastatic spread of cancer. Moreover, the administration of the novel nutraceutical treatment prevented cfChPs from entering healthy cells, and offered a way to mitigate cancer risk, the researchers said.
They claim it will reduce the side effects of cancer treatment by nearly 50 per cent the first time around, and is 30 per cent effective in preventing cancer the second time around. This study confirmed the TMC ACTREC pre-clinical findings that have to be confirmed in a large randomised trial. It is a growing body of research.
Dr R A Badwe, Prof. Emeritus, TMC, told NDTV, that the effect of the nutracetical on cancer treatment side-effects was tested on both rats and humans, but the prevention test was done only on rats. “It will take about five years to complete the human trials for this,” Badwe said.
“Naturally, it has to be validated in human randomised trials in which one group of patients will receive chemotherapy without R-Cu and the other group will receive chemotherapy with R-Cu. Follow-up of these patients will reveal whether R-Cu treatment has prevented metastasis and improved survival,” Mittra told DTE.
R-Cu has been demonstrated in small doses to reduce transplant-related toxicities in patients with multiple myeloma. Over the years, doctors at TMC have prescribed R-Cu to patients with oral, blood, stomach, and brain cancer with promising results, they claimed.
The TMC has entered into a partnership with a manufacturer to commercialise the drug to be potentially prescribed as an adjunct treatment to chemotherapy.
The medication that has been 10 years in the making, is in an oral tablet form. The doctors have applied to the Food Safety and Standards Authority of India (FSSAI) for approval. Following this, it will be available in the market by June or July for just Rs 100.
As the Central Drugs Standard Control Organisation authorises medicine, not the FSSAI, the effectiveness of the drug remains a question.
Rajeev Jayadevan, co-chairman, National Indian Medical Association COVID Task Force, wrote on X, “They used a pro-oxidant combination of copper and resveratrol (found in peanuts, cocoa, and grapes) known to damage DNA by generating Oxygen radicals. Mice had less cfChPs after chemo while on this combination."
“Whether this will translate to real-world outcomes for people with cancer (beyond mice), and what toxicities could occur from its pro-oxidant, DNA-damaging effect, is yet to be determined,” he said.
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