Breakthrough rice bran nanoparticles show promise as affordable and targeted anticancer agent

Plant-derived nanoparticles have demonstrated significant anticancer effects. Researchers recently developed rice bran-derived nanoparticles (rbNPs) that efficiently suppressed cell proliferation and induced programmed cell death of only cancer cells. Furthermore, rbNPs successfully suppressed the growth of tumors in mice having aggressive adenocarcinoma in their peritoneal cavity, without any adverse effects. Given their low production costs and high efficacy, rbNPs hold great promise for developing affordable and safe anticancer agents.

Several types of conventional cancer therapies, such as radiotherapy or chemotherapy, destroy healthy cells along with cancer cells. In advanced stages of cancer, tissue loss from treatments can be substantial and even fatal. Cutting-edge cancer therapies that employ nanoparticles can specifically target cancer cells, sparing healthy tissue. Recent studies have demonstrated that plant-derived nanoparticles (pdNPs) that have therapeutic effects can be an effective alternative to traditional cancer treatments. However, no pdNPs have been approved as anticancer therapeutic agents till date.

Rice bran is a byproduct generated during rice refining process that has limited utility and low commercial value. However, it contains several compounds with anticancer properties, such as γ-oryzanol and γ-tocotrienol. To explore these therapeutic properties of rice bran, a team of researchers led by Professor Makiya Nishikawa from Tokyo University of Science (TUS) in Japan developed nanoparticles from rice bran and tested their effectiveness in mice models. Their study, published in Volume 22 of Journal of Nanobiotechnology on 16 March 2024, was co-authored by Dr. Daisuke Sasaki, Ms. Hinako Suzuki, Associate Professor Kosuke Kusamori, and Assistant Professor Shoko Itakura from TUS.

"In recent years, an increasing number of new drug modalities are being developed. At the same time, development costs associated with novel therapies have increased dramatically, contributing to the burden of medical expenses. To address this issue, we used rice bran, an industrial waste with anticancer properties, to develop nanoparticles," explains Prof. Nishikawa.

The study evaluated the anticancer effects of rice bran-derived nanoparticles (rbNPs), which were obtained by processing and purifying a suspension of Koshihikari rice bran in water. When a cancer cell line named colon26 was treated with rbNPs, cell division was arrested and programmed cell death was induced, indicating strong anticancer effects of the nanoparticles. The observed anticancer activity of rbNPs can be attributed to γ-tocotrienol and γ-oryzanol, that are easily taken up by cancer cells resulting in cell cycle arrest and programmed cell death. Additionally, rbNPs reduced the expression of proteins, such as β-catenin (a protein associated with Wnt signaling pathway involved in cell proliferation) and cyclin D1, which are known to promote cancer recurrence and metastases. Moreover, the rbNPs reduced the expression of β-catenin only in colon26 cells without affecting the non-cancerous cells.

"A key concern in the context of pdNPs is their low pharmacological activity compared to pharmaceutical drugs. However, rbNPs exhibited higher anticancer activity than DOXIL®, a liposomal pharmaceutical formulation of doxorubicin. Additionally, doxorubicin is cytotoxic to both cancer cells and non-cancerous cells, whereas rbNPs are specifically cytotoxic to cancer cells, suggesting that rbNPs are safer than doxorubicin," highlights Prof.Nishikawa.

To confirm the anticancer properties of rbNPs in the living body, the researchers injected rbNPs into mice having aggressive adenocarcinoma in their peritoneal cavity (enclosed by the diaphragm, abdominal muscles, and pelvis and houses organs like intestines, liver, and kidneys). They observed significant suppression of tumor growth with no adverse effects on the mice. Additionally, the rbNPs significantly inhibited metastatic growth of murine melanoma B16-BL6 cells in a lung metastasis mouse model.

Rice bran has several attributes that make it an excellent source of therapeutic pdNPs. Firstly, it is economic as compared to many other sources of pdNPs. Nearly 40% of the rice bran is discarded in Japan, providing a readily available source of raw material. Secondly, the preparation efficiency of rbNPs is higher than that of previously reported pdNPs. Besides being practical and safe as an anticancer therapeutic, the physicochemical properties of rbNPs are very stable. However, a few parameters, such as establishment of separation technologies at the pharmaceutical level, assessing production process control parameters, and evaluation of efficacy and safety in human cancer cell lines and xenograft animal models, must be investigated prior to clinical trials in humans.

In conclusion, rice bran, an agricultural waste product, is a source of therapeutic pdNPs that are affordable, effective, and safe, and has the potential to revolutionize cancer treatment in the future.

Read more at Science Daily

Researchers turn back the clock on cancer cells to offer new treatment paradigm

St. Jude Children's Research Hospital scientists reversed an aggressive cancer, reverting malignant cells towards a more normal state. Rhabdoid tumors are an aggressive cancer which is missing a key tumor suppressor protein. Findings showed that with the missing tumor suppressor, deleting or degrading the quality control protein DCAF5 reversed the cancer cell state. These results suggest a new approach to curing cancer -- returning cancerous cells to an earlier, more normal state rather than killing cancer cells with toxic therapies -- may be possible. The results were published today in Nature.

"Rather than making a toxic event that kills rhabdoid cancer, we were able to reverse the cancer state by returning the cells toward normal," said senior author Charles W.M. Roberts, MD, PhD, Executive Vice President and St. Jude Comprehensive Cancer Center director. "This approach would be ideal, especially if this paradigm could also be applied to other cancers."

"We found a dependency which actually reverses the cancer state," said first author Sandi Radko-Juettner, PhD, a former St. Jude Graduate School of Biomedical Sciences student, now a Research Program Manager for the Hematological Malignancies Program at St. Jude. "Standard cancer therapies work by causing toxicities that also damage healthy cells in the body. Here, it appears that we're instead fixing the problem caused by the loss of a tumor suppressor in this rhabdoid cancer."

Drugging the un-targetable

In many cancers, there is no easily druggable target. Often, these cancers are caused by a missing tumor suppressor protein, so there is nothing to target directly as the protein is missing. Loss of tumor suppressors is much more common than a protein gaining the ability to drive cancer. Consequently, finding a way to intervene therapeutically in these tumors is a high priority. The researchers were looking for a way to treat an aggressive set of cancers caused by the loss of the tumor suppressor protein SMARCB1 when they found a new approach to treatment.

The St. Jude group found a little-studied protein, DCAF5, was essential to rhabdoid tumors missing SMARCB1. Initially, they identified DCAF5 as a target, using the Dependency Map (DepMap) portal, a database of cancer cell lines and the genes critical for their growth. DCAF5 was a top dependency in rhabdoid tumors. After the initial finding, the scientists genetically deleted or chemically degraded DCAF5. The cancer cells reverted to a non-cancerous state, persisting even in a long-term mouse model.

"We saw a spectacular response," Roberts said. "The tumors melted away."

Removing quality control to reverse cancer

Normally, SMARCB1 is an essential component of a larger chromatin-regulating complex of proteins called the SWI/SNF complex. Unexpectedly, the study found that in the absence of SMARCB1, DCAF5 recognizes SWI/SNF as abnormal and destroys the complex. When DCAF5 degrades them, the researchers showed that SWI/SNF re-forms and maintains its ability to open chromatin and regulate gene expression. While the SWI/SNF activity level in the absence of SMARCB1 was to a lesser extent than usual, it was nonetheless sufficient to reverse the cancer state fully.

"DCAF5 is doing a quality control check to ensure that these chromatin machines are built well," Roberts said. "Think of a factory assembling a machine. You need quality checks to examine and find faults and to pull it off the line if it doesn't meet standards. DCAF5 is doing such quality assessments for the assembly of SWI/SNF complexes, telling the cell to get rid of complexes if SMARCB1 is absent."

"The mutation of SMARCB1 shuts off gene programs that prevent cancer. By targeting DCAF5, we're turning those gene programs back on," Radko-Juettner said. "We're reversing the cancer state because the cell is becoming more 'normal' when these complexes aren't targeted for destruction by DCAF5."

Future therapeutic opportunities to reverse cancer

"From a therapeutic perspective, our results are fascinating," Radko-Juettner said. "DCAF5 is part of a larger family of DCAF proteins that have been shown to be drug targetable. We showed that when DCAF5 is absent, mice had no discernable health effects, so we could potentially target DCAF5. This can kill the cancer cells but shouldn't affect healthy cells. Targeting DCAF5 thus has the potential to avoid the off-target toxicity of radiation or chemotherapy, making it a promising therapeutic avenue to pursue."

Beyond DCAF5, the findings could have implications for other cancers driven by the loss of a tumor suppressor.

Read more at Science Daily