Eugenol Promotes Apoptosis in Leukemia Cells via Targeting the Mitochondrial Biogenesis PPRC1 Gene.

Acute myeloid leukemia (AML) is a highly heterogenous and aggressive myeloid neoplasm. To sustain growth and survival, AML cells, like other neoplasms, require energy. This process is orchestrated by mitochondria and is under the control of several genes, such as PPRC1 (PRC), a member of the PGC-1 family, which is a key player in the transcription control of mitochondrial biogenesis. We have shown here that eugenol inhibits cell growth and promotes apoptosis through the mitochondrial pathway in AML cell lines as well as in cells from AML patients but not in cells from healthy donors. Similar effects were also observed on cytarabine-resistant AML cells. Interestingly, eugenol downregulated PPRC1 at both the protein and mRNA levels and reduced mitochondrial membrane potential in AML cells. We have also shown that PPRC1 expression is higher in cancer cells from blood, breast, and other types of cancer relative to normal cells, and high PPRC1 levels correlate significantly with short overall survival (OS). In addition, PPRC1 gene mutations significantly correlate with short OS and/or disease-free survival in several cancers. PPRC1 mutations also correlated significantly with poor OS (p < 0.0001) when tested in a total of 23,456 cancer patients. These findings suggest an oncogenic role of PPRC1 in various types of cancer and the possible eugenol-targeting of this gene for the treatment of AML patients, especially those exhibiting resistance to cytarabine.