RESUMEN
Natural remedies have been indispensable to traditional medicine practices for generations, offering therapeutic solutions for various ailments. In modern times, these natural products continue to play a pivotal role in the discovery of new drugs, especially for cancer treatment. The marine ecosystem offers a wide range of plants with potential anticancer activities due to their distinct biochemical diversity and adaptation to extreme situations. The seagrass Halodule uninervis is rich in diverse bioactive metabolites that bestow the plant with various pharmacological properties. However, its anticancer activity against invasive triple-negative breast cancer (TNBC) is still poorly investigated. In the present study, the phytochemical composition of an ethanolic extract of H. uninervis (HUE) was screened, and its antioxidant potential was evaluated. Moreover, the anticancer potential of HUE against MDA-MB-231 cells was investigated along with the possible underlying mechanisms of action. Our results showed that HUE is rich in diverse phytochemicals that are known for their antioxidant and anticancer effects. In MDA-MB-231 cells, HUE targeted the hallmarks of cancer, including cell proliferation, adhesion, migration, invasion, and angiogenesis. The HUE-mediated anti-proliferative and anti-metastatic effects were associated with the downregulation of the proto-oncogenic STAT3 signaling pathway. Taken together, H. uninervis could serve as a valuable source for developing novel drugs targeting TNBC.
RESUMEN
Natural products have long been utilized in traditional medicine as remedies to improve health and treat illnesses, and have had a key role in modern drug discovery. Recently, there has been a revived interest in the search for bioactives from natural sources as alternative or complementary modalities to synthetic medicines; especially for cancer treatment, which incidence and mortality rates are on the rise worldwide. Ziziphus nummularia has been widely used in traditional medicine for the treatment of various diseases. Its traditional uses and numerous ethnopharmacological properties may be attributed to its richness in bioactive metabolites. However, its phytochemical composition or chemopreventive effects against the aggressive triple-negative breast cancer (TNBC) are still poorly explored. Here, phytochemical composition of an ethanolic extract of Z. nummularia leaves (ZNE) and its chromatographically isolated fractions was identified both qualitatively by spectrophotometric assays and analytically by HPLC-PDA-MS/MS. The anti-proliferative effects of ZNE were tested in several cancer cell lines, but we focused on its anti-TNBC effects since they were not explored yet. The anti-cancerous potential of ZNE and its fractions was tested in vitro in MDA-MB-231, a TNBC cell line. Results showed that ZNE and its Fraction 6 (F6) reduced the viability of MDA-MB-231 cells. F6 decreased MDA-MB-231 viability more than crude ZNE or its other fractions. ZNE and F6 are rich in phytochemicals and HPLC-PDA-MS/MS analysis identified several metabolites that were previously reported to have anti-cancerous effects. Both ZNE and F6 showed potent antioxidant capacity in the DPPH assay, but promoted reactive oxygen species (ROS) production in MDA-MB-231 cells; an effect which was blunted by the antioxidant N-acetyl cysteine (NAC). NAC also blunted ZNE- and F6-induced reduction in TNBC cell viability. We also demonstrated that ZNE and F6 induced an arrest of the cell cycle, and triggered apoptosis- and autophagy-mediated cell death. ZNE and F6 inhibited metastasis-related cellular processes by modifying cell migration, invasion, and adhesion. Taken together, our findings reveal that Z. nummularia is rich in phytochemicals that can attenuate the malignant phenotype of TNBC and may offer innovative avenues for the discovery of new drug leads for treatment of TNBC and other cancers.
RESUMEN
Anchusa strigosa Banks and Sol. is a rough flowering plant of the Boraginaceae family native to Eastern Mediterranean region that is widely used in traditional herbal medicine, mainly for the treatment of wounds, abdominal pain, and arthritis, to name a few. This article aims to gather knowledge related to the medicinal properties of A. strigosa. Specifically, it summarizes its traditional uses and pharmacological activities in the treatment of various diseases. Moreover, its botanical, ecological, and phytochemical characteristics are also discussed. Research showed that this plant is rich in pyrrolizidine alkaloids, particularly in the leaves. Other bioactive metabolites identified in this plant include flavonoids, phenolic acids, triterpenes, organic acids, and volatile organic compounds. These phytochemicals are responsible for the reported pharmacological properties of A. strigosa, including antimicrobial, antioxidant, anticancer, anti-inflammatory, antiarthritic, gastric protective, antidiabetic, and pro-wound healing. This warrants further investigation into the molecular mechanism of action behind the observed effects to elucidate its therapeutic potential. Nevertheless, more research on this plant is needed to ensure its efficacy and safety.
RESUMEN
Pancreatic cancer is a highly aggressive malignancy and a leading cause of cancer-related deaths worldwide. Moreover, the incidence and mortality rates for pancreatic cancer are projected to keep increasing. A major challenge in the treatment of pancreatic cancer is the lack of effective screening approaches, which contributes to its poor prognosis, indicating the need for new treatment regimens and alternative therapies, such as herbal medicine. The medicinal plant A. strigosa, which is widely distributed in the Eastern Mediterranean region, is a short prickly plant from the Boraginaceae family that has been widely used in traditional medicine for treating various diseases. Nevertheless, its effect on human pancreatic cancer remains poorly investigated. In the present study, we screened the phytochemical content of Anchusa strigosa aqueous extracts obtained by maceration and ultrasound-assisted methods (ASM and ASU, respectively) and evaluated their antioxidant effects. We also investigated their anticancer effects and possible underlying mechanisms. The results show that both extracts were rich in bioactive molecules, with slight differences in their composition. Both extracts exhibited remarkable antioxidant potential and potent radical-scavenging activity in vitro. Additionally, non-cytotoxic concentrations of both extracts attenuated cell proliferation in a time- and concentration-dependent manner, which was associated with a decrease in the proliferation marker Ki67 and an induction of the intrinsic apoptotic pathway. Furthermore, the extracts increased the aggregation of pancreatic cancer cells and reduced their migratory potential, with a concomitant downregulation of integrin ß1. Finally, we showed that the ASM extract caused a significant decrease in the levels of COX-2, an enzyme that has been linked to inflammation, carcinogenesis, tumor progression, and metastasis. Taken together, our findings provide evidence that A. strigosa extracts, particularly the extract obtained using the maceration method, have a potential anticancer effect and may represent a new resource for the design of novel drugs against pancreatic cancer.
