Petiveria alliacea Reduces Tumor Burden and Metastasis and Regulates the Peripheral Immune Response in a Murine Myeloid Leukemia Model

Abstract

The poor response, adverse effects and drug resistance to treatment of acute myeloid leukemia (AML) have led to searching for safer and more effective therapeutic alternatives. We previously demonstrated that the alcoholic extract of Petiveria alliacea (Esperanza) has a significant in vitro antitumor effect on other tumor cells and also the ability to regulate energy metabolism. We evaluated the effect of the Esperanza extract in vitro and in vivo in a murine model of AML with DA-3/ER-GM cells. First, a chemical characterization of the extract was conducted through liquid and gas chromatography coupled with mass spectrometry. In vitro findings showed that the extract modulates tumor metabolism by decreasing glucose uptake and increasing reactive oxygen species, which leads to a reduction in cell proliferation. Then, to evaluate the effect of the extract in vivo, we standardized the mouse model by injecting DA-3/ER-GM cells intravenously. The animals treated with the extract showed a lower percentage of circulating blasts, higher values of hemoglobin, hematocrit, and platelets, less infiltration of blasts in the spleen, and greater production of cytokines compared to the control group. These results suggest that the antitumor activity of this extract on DA-3/ER-GM cells can be attributed to the decrease in glycolytic metabolism, its activity as a mitocan, and the possible immunomodulatory effect by reducing tumor proliferation and metastasis.

Effect of Petiveria alliacea Extracts on Metabolism of K562 Myeloid Leukemia Cells

“…Notably, it has been documented that the inhibition of glycolysis can lead to elevated glucose levels [28][29][30]. We previously showed a reduction in glycolysis in a breast cancer cellular model (4T1) and an in vivo leukemia model [18,21]. This reduction can be attributed to the primary compounds previously reported in the extract, such as isoleucine and valine, which have shown the ability to decrease proliferation and tumor growth by upregulating the tumor suppressor gene PTEN.…”

“…Previously, the role of P. alliacea in mitochondrial function was demonstrated, mediated by an ethyl acetate fraction which, in vitro, induces apoptosis in 4T1 cells, activates caspase 3, and causes DNA fragmentation [16,18]. It is also worth noting that an additional impact on mitochondria possibly induced by malic acid has been previously described with the Esperanza extract [21]. Malic acid is known to inhibit succinate dehydrogenase, an enzyme that plays a central role in the TCA cycle and as part of complex II in the electron transport chain [35].…”

“…Previous studies have demonstrated that increased carnitine-dependent fatty acid uptake into mitochondria can induce mitochondrial dysfunction [41]. In addition to the primary compounds, the secondary compounds previously characterized in the extract [21] also exhibit various anti-tumor activities: ferulic acid induces apoptosis and inhibits tumor necrosis factor-α and Akt/mTOR signaling in leukemic cells [42]; cinnamic acid induces apoptotic cell death and alteration of the cytoskeleton in human melanoma cells [43]; and quinic acid, an antioxidant, exhibits anti-tumor activity through the induction of apoptosis and decreased angiogenesis in breast cancer cells [44]. Finally, a widely studied compound is gallic acid, a phenolic compound that modulates genes involved in the cell cycle, metastasis, and angiogenesis, leading to the inhibition of tumor cell growth; it also inhibits key signaling pathways for proliferation such as NF-KB and Akt [45][46][47].…”

Exploring the Therapeutic Potential of Petiveria alliacea L. Phytochemicals: A Computational Study on Inhibiting SARS-CoV-2’s Main Protease (Mpro)

“…In this study, we collected 150 phytocompounds for Petiveria alliacea L. through a systematic literature review [24,[30][31][32][33] and using the online database IMPPAT 2.0 [34] (https://cb.imsc.res.in/imppat/home, accessed on 10 January 2024). The 3D structure of these phytocompounds was extracted from the PubChem database [35].…”

Comparative Analysis of Bacteria, Fungi, and Arbuscular Mycorrhizal Fungi in Medicinal Plants Lippia alba and Petiveria alliacea in Colombia

“…Several studies have examined the anti-carcinogenic effects of their essential oils, in the case of L. alba, research has shown its potential in halting the cell cycle and inducing apoptosis in liver and lung cancer cells [14], colon and prostate cancer cells [15], leukemia cells [16], and gastric carcinoma cells [17]. Similarly, P. alliacea has been found to trigger cell apoptosis and reduce the growth capability of breast cancer cell colonies [18], along with diminishing tumor burden and myeloid leukemia metastasis [19]. Despite the significance of these plants and the evidence suggesting that the interaction between medicinal plants and the microbiome results in the production of phytotherapeutic compounds [20][21][22], no studies have been conducted on the microbiome associated with L. alba and P. alliacea.…”