&lt;p&gt;Nanodelivery and anticancer effect of a limonoid, nimbolide, in breast and pancreatic cancer cells&lt;/p&gt;

Patra, Amarendra; Satpathy, Swaha; Hussain, Muhammad Delwar

doi:10.2147/ijn.s208540

Cited by 28 publications

(14 citation statements)

References 53 publications

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“…Its incidence ranks tenth among malignant tumors, and its mortality ranks fourth among the causes of death from malignant tumors [8] . In recent years, more and more scholars have devoted themselves to researching anti‐pancreatic cancer drugs and confirmed that limonoids have certain anti‐pancreatic cancer activity [6,9–11] . Therefore, we also conducted research on the anti‐pancreatic cancer activity of the isolated limonoids in this study.…”

Section: Introductionmentioning

confidence: 82%

Two New Limonoids from the Fruits of Melia azedarach (Meliaceae)

Wang

Xia

et al. 2020

Chemistry & Biodiversity

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Two new limonoids, trichilinin M (1) and ohchinin benzoate (2), along with two known limonoids, 12‐hydroxyamoorastatone (3) and mesendanin H (4), were isolated from the fruits of Melia azedarach Linn. The structures of new limonoids were determined by analyses of HR‐ESI‐MS, 1D and 2D NMR (HSQC, HMBC and NOESY) data. All compounds were evaluated against human pancreatic cancer PANC1 cells and the results showed that compounds 3–4 exhibited substantial cytotoxic activity (3: IC50=4.55 μM; 4: IC50=7.54 μM), and compounds 1–2 exhibited moderate cytotoxicity (1: IC50=27.06 μM; 2: IC50=21.17 μM).

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Section: Introductionmentioning

confidence: 82%

Two New Limonoids from the Fruits of Melia azedarach (Meliaceae)

Wang

Xia

et al. 2020

Chemistry & Biodiversity

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“…Overall, the untargeted approach enabled the putative annotation of 279 compounds (excluding isobaric compounds), and the resulting dataset is reported in the Supplementary Materials, together with the relative abundance and mass spectra of each compound. The detected phytochemicals belonged to different chemical classes, such as flavonoids (108), limonoids/terpenoids (59), phenolic acids (49), lower-molecular-weight (LMW) phenolics (39), lignans (17) and stilbenes (7). In particular, anthocyanins (pigmented flavonoids) were primarily identified in T. ciliata, up to 104.16 mg Eq./g dry matter (Table 1) and mainly represented by cyanidin, pelargonidin, malvidin, peonidin, petunidin, delphinidin and their glycosides.…”

Section: Phytochemical Profiling Of Meliaceae Extracts Using Uhplc-qt...mentioning

confidence: 99%

“…For example, the Egyptian flaxseed, especially Giza-9, and its dietary formulations are enriched with lignans and exerted an in vitro and in vivo anticancer effect on a human breast cancer cell line and in mice bearing tumors [58]. Nanoformulated nimbolide, is characterized by its sustained release for more than 6 days in PBS (pH 7.4) and also exerted enhanced cytotoxicity about two-to three-fold in both breast and pancreatic cancer cell lines compared with free nimbolide [59].…”

Section: Pearson's Correlations Between Phytochemical Profile and Bio...mentioning

confidence: 99%

The Untargeted Phytochemical Profile of Three Meliaceae Species Related to In Vitro Cytotoxicity and Anti-Virulence Activity against MRSA Isolates

et al. 2022

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Background: A high mortality rate is associated with about 80% of all infections worldwide, mainly due to antimicrobial resistance. Various antimicrobial and cytotoxic activities have been proposed for Meliaceae species. This study aimed to evaluate the in vitro anti-virulence and cytotoxic effect of the leaf extracts of Aphanamixis polystachya, Toona ciliata and Melia azedarach against five MRSA strains and on three cancer cell lines, followed by biological correlation to their encompassed phytoconstituents. Material and Methods: We explored three plants of this family against a panel of Methicillin-resistant Staphylococcus aureus (MRSA) strains and several cancer cell lines to select the most promising candidates for further in vivo and preclinical studies. The phytochemical composition was evaluated by UHPLC–QTOF–MS untargeted profiling. Cell viability was assessed by SRB assay. Minimum Inhibitory Concentration was carried out by using the agar micro-dilution technique. Inhibition of biofilm formation and preformed biofilm disruption were assessed spectrophotomertically, according to the Sultan and Nabil method (2019). Results: A total of 279 compounds were putatively annotated to include different phytochemical classes, such as flavonoids (108), limonoids/terpenoids (59), phenolic acids (49) and lower-molecular-weight phenolics (39). A. polystachya extract showed the most potent cytotoxic activity against Huh-7, DU-145 and MCF-7 cell lines (IC50 = 3, 3.5 and 13.4 µg mL−1, respectively), followed by M. azedarach, with no effect recorded for T. ciliata extract. Furthermore, both A. polystachya and M. azedarach extracts showed promising anti-virulence and antimicrobial activities, with A. polystachya being particularly active against MRSA. These two latter extracts could inhibit and disrupt the biofilm, formed by MRSA, at sub-lethal concentrations. Interestingly, the extracts inhibited hemolysin-α enzyme, thus protecting rabbit RBCs from lysis. A. polystachya extract reduced the pigmentation and catalase enzyme activity of tested pigmented strains better than M. azedarach at both tested sub-MICs. Consequently, susceptibility of the extract-treated cells to oxidant killing by 200 mM H2O2 increased, leading to faster killing of the cells within 120 min as compared to the extract-non-treated cells, likely due to the lower antioxidant-scavenging activity of cells exhibiting less staphyloxanthin production. Conclusion: These findings suggested that both A. polystachya and M. azedarach natural extracts are rich in bioactive compounds, mainly limonoids, phenolics and oxygenated triterpenoids, which can combat MRSA biofilm infections and could be considered as promising sources of therapeutic cytotoxic, antibiofilm and anti-virulence agents.

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“…In many degenerative disorders including diabetes, and various types of cancers including pancreatic cancer, the potential of neem plant extract is considered to be due to the abundant presence of the active limonoid, azadirachtin. Azadirachtin and related limonoids have been shown to protect β-cells from oxidative and inflammatory stress-induced cytotoxicity by manipulating the cell signalling kinases and anti-inflammatory responses [ 24 , 25 , 26 , 27 , 28 ]. The present study focuses on the identification of biochemical markers in Rin-5F cells affected by LPS treatment and the mechanism of protection of cytotoxicity by AZD.…”

Section: Introductionmentioning

confidence: 99%

Azadirachtin Attenuates Lipopolysaccharide-Induced ROS Production, DNA Damage, and Apoptosis by Regulating JNK/Akt and AMPK/mTOR-Dependent Pathways in Rin-5F Pancreatic Beta Cells

John

Raza

2021

Biomedicines

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Pancreatic inflammation and the resulting cellular responses have been implicated in pancreatitis, diabetes, and pancreatic cancer. Inflammatory responses due to the bacterial endotoxin, lipopolysaccharide (LPS), have been demonstrated to alter cellular metabolism, autophagy, apoptosis, and cell proliferation in different cell populations, and hence increases the risks for organ toxicity including cancer. The exact molecular mechanism is however not clear. In the present study, we investigated the role and mechanism of an antioxidant, azadirachtin (AZD), a limonoid extracted from the neem tree (Azadirachta indica), against LPS-induced oxidative stress in the pancreatic β-cell line, Rin-5F. We demonstrated that cells treated with LPS (1 µg/mL for 24 h) showed increased reactive oxygen species (ROS) production, DNA damage, cell cycle arrest, and apoptosis. Our results also showed that LPS induced alterations in the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathways, suppressing autophagy and augmenting apoptosis. Treatment with Azadirachtin (25 µM for 24 h), on the other hand, rendered some degree of protection to the pancreatic cells from apoptosis by inducing the autophagy signals required for cell survival. These results may have significance in elucidating the mechanisms of pancreatic β-cell survival and death by balancing the molecular communication between autophagy and apoptosis under inflammatory and pathological conditions.

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<p>Nanodelivery and anticancer effect of a limonoid, nimbolide, in breast and pancreatic cancer cells</p>

Cited by 28 publications

References 53 publications

Two New Limonoids from the Fruits of Melia azedarach (Meliaceae)

Two New Limonoids from the Fruits of Melia azedarach (Meliaceae)

The Untargeted Phytochemical Profile of Three Meliaceae Species Related to In Vitro Cytotoxicity and Anti-Virulence Activity against MRSA Isolates

Azadirachtin Attenuates Lipopolysaccharide-Induced ROS Production, DNA Damage, and Apoptosis by Regulating JNK/Akt and AMPK/mTOR-Dependent Pathways in Rin-5F Pancreatic Beta Cells

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