Overcoming the Challenges of Phytochemicals in Triple Negative Breast Cancer Therapy: The Path Forward

Alaouna, Mohammed; Penny, Clement; Hull, Rodney; Molefi, Thulo; Chauke-Malinga, Nkhensani; Khanyile, Richard; Makgoka, Malose; Bida, Meshack; Dlamini, Zodwa

doi:10.3390/plants12122350

Cited by 4 publications

(1 citation statement)

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“…In fact, often time plant extracts or phytochemicals do not show in vivo efficacy despite their potent in vitro effects. Despite the promise of phytochemicals in TNBC therapy, they still have several limitations that hinder their clinical application for TNBC therapy (Alaouna et al, 2023). Future investigations should be directed to uncover the anti-TNBC potential of ZNE and F6 in an in vivo animal model.…”

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%

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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A Systematic Review of Application of Resveratrol and the Recent Progress of the Drug Delivery System

2024

BIO Web Conf.

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Background: Resveratrol is a natural compound in plants like grapes and peanuts, it’s an antioxidant used in supplements and medicine. It’s a colorless crystal soluble in organic solvents, with poor water solubility but high cell membrane permeability. It exists in cis and trans forms. Objective: To explore the background of resveratrol, this review comprehensively summarizes the recent advances in resveratrol including its application in cancer, type-2 diabetes mellitus, vascular disease, and the delivery system. Data sources: We performed a narrative review, based on relevant articles written in English from a PubMed search, using the following search terms: “resveratrol”, and “bioavailability” and “bone health” or “cancer”, or “cardiovascular”, or “diabetes” or “estrogen” or “weight management” or “metabolism”. Results: Cancer’s aggressive nature requires multiple therapies, but they often cause side effects. Resveratrol (RSV) is a promising cancer treatment due to its fewer adverse effects. It inhibits cancer cell growth and promotes cell death by targeting specific pathways. Recent studies also examine the relationship between polyphenol intake and diabetes markers in overweight/obese individuals with metabolic syndrome. Increased polyphenol intake may reduce these markers, particularly in those with pre-diabetes. However, findings vary due to study heterogeneity. Vascular endothelial dysfunction is a critical factor in cardiovascular diseases. Phytochemical compounds, like resveratrol have antioxidative and anti-inflammatory properties that protect the cardiovascular system. Resveratrol prevents inflammation, reduces oxidative stress, and improves endothelial function, making it a promising therapy for cardiovascular diseases. To face the limitation like its low solubility and rapid metabolism, the drug delivery system has also been studied in this review. Various nanodelivery systems, including liposomes, polymeric nanoparticles, and inorganic nanoparticles, have shown promise in overcoming these challenges by improving solubility, biocompatibility, and therapeutic efficacy. Conclusions: While recent advancements in resveratrol’s application show promise, further research is needed to optimize nanoformulations, validate efficacy in vivo, and tackle challenges like scalability and toxicity. Overall, these developments offer a promising path to maximize resveratrol’s therapeutic potential in clinical settings.

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Breaking the barriers: Overcoming cancer resistance by targeting the NLRP3 inflammasome

Pazhouhesh Far,

Hajiheidari Varnousafaderani,

Faghihkhorasani

et al. 2024

British J Pharmacology

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Inflammation has a pivotal role in the initiation and progression of various cancers, contributing to crucial processes such as metastasis, angiogenesis, cell proliferation and invasion. Moreover, the release of cytokines mediated by inflammation within the tumour microenvironment (TME) has a crucial role in orchestrating these events. The activation of inflammatory caspases, facilitated by the recruitment of caspase‐1, is initiated by the activation of pattern recognition receptors on the immune cell membrane. This activation results in the production of proinflammatory cytokines, including IL‐1β and IL‐18, and participates in diverse biological processes with significant implications. The NOD‐Like Receptor Protein 3 (NLRP3) inflammasome holds a central role in innate immunity and regulates inflammation through releasing IL‐1β and IL‐18. Moreover, it interacts with various cellular compartments. Recently, the mechanisms underlying NLRP3 inflammasome activation have garnered considerable attention. Disruption in NLRP3 inflammasome activation has been associated with a spectrum of inflammatory diseases, encompassing diabetes, enteritis, neurodegenerative diseases, obesity and tumours. The NLRP3 impact on tumorigenesis varies across different cancer types, with contrasting roles observed. For example, colorectal cancer associated with colitis can be suppressed by NLRP3, whereas gastric and skin cancers may be promoted by its activity. This review provides comprehensive insights into the structure, biological characteristics and mechanisms of the NLRP3 inflammasome, with a specific focus on the relationship between NLRP3 and tumour‐related immune responses, and TME. Furthermore, the review explores potential strategies for targeting cancers via NLRP3 inflammasome modulation. This encompasses innovative approaches, including NLRP3‐based nanoparticles, gene‐targeted therapy and immune checkpoint inhibitors.

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Overcoming the Challenges of Phytochemicals in Triple Negative Breast Cancer Therapy: The Path Forward

Cited by 4 publications

References 173 publications

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

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

A Systematic Review of Application of Resveratrol and the Recent Progress of the Drug Delivery System

Breaking the barriers: Overcoming cancer resistance by targeting the NLRP3 inflammasome

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