Photo by Rhoda Baer
Preclinical research suggests that compounds derived from Himalayan rhubarb could potentially treat leukemias and other cancers.
These compounds, physcion and S3, effectively inhibited 6PGD, a metabolic enzyme that is upregulated in several types of cancer cells.
In addition, physcion and S3 reduced cancer cell viability in vitro and decreased tumor size in vivo—without harming normal cells or exhibiting obvious toxicity.
Jing Chen, PhD, of Emory University School of Medicine in Atlanta, Georgia, and his colleagues described this research in Nature Cell Biology.
The team set out to find 6PGD inhibitors because 6PGD is part of the pentose phosphate pathway, which supplies cellular building blocks for rapid growth. And previous research had revealed increased 6PGD activity in several types of cancer cells.
“This is part of the Warburg effect, the distortion of cancer cells’ metabolism,” Dr Chen said. “We found that 6PGD is an important metabolic branch point in several types of cancer cells.”
Specifically, the investigators found that knocking down 6PGD decreased proliferation in a handful of human cancer cell lines—leukemia (K562), lung cancer (H1299, H157, and H322), and head and neck cancer (212LN).
But 6PGD knockdown did not affect normal proliferating keratinocyte HaCaT cells.
When the team screened for 6PGD inhibitors, they identified physcion—an anthraquinone originally isolated from Himalayan rhubarb—and its derivative, S3.
Experiments showed that physcion decreases cell viability in a range of cancer cell lines—K562, H1299, A549 (lung), and 212LN—in a dose-dependent manner. But the compound did not significantly affect proliferating control cells—human dermal fibroblasts (HDFs) and immortalized human melanocyte PIG1 cells.
Similarly, S3 inhibited the viability of K562 and H1299 cells but not proliferating PIG1 and HDF cells.
S3 also decreased tumor growth in mouse models of leukemia, lung cancer, and head and neck cancer. However, the treatment did not affect body weight, serum chemistry, complete blood counts, or hematopoietic properties in the mice.
Finally, the investigators found that physcion and S3 inhibit 6PGD in human primary leukemia cells (B-cell acute lymphoblastic leukemia), thereby leading to decreased cell viability.
And neither compound affected the viability of mononucleocytes in peripheral blood samples or CD34+ progenitors isolated from the bone marrow samples of healthy donors.
