Intercellular Communication in Cancer

Shaito, Abdullah; Saliba, Jessica; Obeid, Joelle; El-Harakeh, Mohammad; Hajj, Hiba El; El-Sabban, Marwan

doi:10.1007/978-3-030-80962-1_39-1

Cited by 1 publication

(1 citation statement)

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“…Once cancer cells have migrated and adhered to secondary tissues, invasion processes are initiated. Degradation of the ECM, by proteinases particularly MMPs, is not only required for cell migration and invasion at the initial stages of metastasis where the primary tumor cells need to extravasate, but also at secondary tumor sites where the tumor cells need to intravasate to secondary tumor sites (Saliba et al, 2023;Shaito et al, 2023). In particular, the protease MMP-9 is overexpressed in breast cancer and its expression is associated with a higher incidence of metastasis, and therefore it is used as a prognosis marker (Joseph et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Fractionation and phytochemical composition of an ethanolic extract of Ziziphus nummularia leaves: antioxidant and anticancerous properties in human triple negative breast cancer cells

Abdallah,

Shaito,

Badran

et al. 2024

Front. Pharmacol.

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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.

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Section: Discussionmentioning

confidence: 99%