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Oral cancer is a severe health problem that accounts for an alarmingly high number of fatalities worldwide. Withania somnifera (L.) Dunal has been extensively studied against various tumor cell lines from different body organs, rarely from the oral cavity. We thus investigated the cytotoxicity of W. somnifera fruits (W-F) and roots (W-R) hydromethanolic extracts and their chromatographic fractions against oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingiva), HSC-2, HSC-3, and HSC-4 (derived from tongue)] and three normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF), and human pulp cells (HPC)] in comparison to standard drugs. The root polar ethyl acetate (W-R EtOAc) and butanol (W-R BuOH) fractions exhibited the strongest cytotoxicity against the Ca9-22 cell line (CC50 = 51.8 and 40.1 µg/mL, respectively), which is relatively the same effect as 5-FU at CC50 = 69.4 µM and melphalan at CC50 = 36.3 µM on the same cancer cell line. Flow cytometric analysis revealed changes in morphology as well as in the cell cycle profile of the W-R EtOAc and W-R BuOH-treated oral cancer Ca9-22 cells compared to the untreated control. The W-R EtOAc (125 µg/mL) exerted morphological changes and induced subG1 accumulation, suggesting apoptotic cell death. A UHPLC MS/MS analysis of the extract enabled the identification of 26 compounds, mainly alkaloids, withanolides, withanosides, and flavonoids. Pharmacophore-based inverse virtual screening proposed that BRD3 and CDK2 are the cancer-relevant targets for the annotated withanolides D (18) and O (12), and the flavonoid kaempferol (11). Molecular modeling studies highlighted the BRD3 and CDK2 as the most probable oncogenic targets of anticancer activity of these molecules. These findings highlight W. somnifera's potential as an affordable source of therapeutic agents for a range of oral malignancies. [ABSTRACT FROM AUTHOR]

Polyphenols have a variety of phenolic hydroxyl and carbonyl functionalities that enable them to scavenge many oxidants, thereby preserving the human redox balance and preventing a number of oxidative stress-related chronic degenerative diseases. In our ongoing investigation of polyphenol-rich plants in search of novel molecules, we resumed the investigation of Lawsonia inermis L. (Lythraceae) or henna, a popular ancient plant with aesthetic and therapeutic benefits. The leaves' 70% aq acetone extract was fractionated on a Diaion HP-20 column with different ratios of H2O/an organic solvent. Multistep gel chromatographic fractionation and HPLC purification of the Diaion 75% aq MeOH and MeOH fractions led to a new compound (1) along with tannin-related metabolites, benzoic acid (2), benzyl 6′-O-galloyl-β-D-glucopyranoside (3), and ellagic acid (4), which are first isolated from henna. Repeating the procedures on the Diaion 50% aq MeOH eluate led to the first-time isolation of two O-glucosidic ellagitannins, heterophylliin A (5), and gemin D (6), in addition to four known C-glycosidic ellagitannins, lythracin D (7), pedunculagin (8), flosin B (9), and lagerstroemin (10). The compound structures were determined through intensive spectroscopic investigations, including HRESIMS, 1D (1H and 13C) and 2D (1H–1H COSY, HSQC, HMBC, and NOESY) NMR, UV, [α]D, and CD experiments. The new structure of 1 was determined to be a megastigmane glucoside gallate; its biosynthesis from gallic acid and a β-ionone, a degradative product of the common metabolite β-carotin, was highlighted. Cytotoxicity investigations of the abundant ellagitannins revealed that lythracin D2 (7) and pedunculagin (8) are obviously more cytotoxic (tumor specificity = 2.3 and 2.8, respectively) toward oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9-22) than normal human oral cells (HGF, HPC, and HPLF). In summary, Lawsonia inermis is a rich source of anti-oral cancer ellagitannins. Also, the several discovered polyphenolics highlighted here emphasize the numerous biological benefits of henna and encourage further clinical studies to profit from their antioxidant properties against oxidative stress-related disorders. [ABSTRACT FROM AUTHOR]

Aim: The objective of this research is to present a phytochemical profile of Fagonia arabica and to investigate the cytotoxic potential of its extracts against breast, oral, and lung cancer cell lines using MTT assay and dual staining-based mechanistic analysis. Methods: The progressive extraction of F. arabica was carried out using the Soxhlet extraction technique. The total phenolic and flavonoid content was calculated as part of the phytochemical profiling performed using GCMS and LCMS methods. The MTT assay was utilized to assess the cytotoxicity against normal L929 cells, as well as malignant A549, MCF-7, and KB-3-1cell lines. Results: The phenolic compounds and flavonoids were the two main elements of the F. arabica methanolic extract, with 1323 µg GAE/g of dry weight and 523.07 µg QE/g of dry weight, respectively. The presence of the functional phytochemicals was verified by GCMS and LCMS analyses. Toxicity testing on the L929 cell line found that the F. arabica methanol extract was the least harmful, with the highest IC50 (296.11 µg/mL). The MTT assay for cell viability against MCF-7 and KB-3-1 yielded significant results, with IC50 values of 135.02 µg/mL and 195.21 µg/mL, respectively. The aqueous extract exhibited significant cytotoxicity against the A549 cell lines (IC50 116.06 µg/mL). The molecular marker analyses using dual staining revealed that the methanolic extract successfully triggered apoptosis in the different cancer cells tested. Conclusion: The present data suggest that the methanol extract of F. arabica has substantial cytotoxic action against lung, breast, and oral cancer cell lines. Thus, F. Arabica would be a promising source of anticancer medicines, warranting more research to identify the lead molecules with anticancer properties. [ABSTRACT FROM AUTHOR]

Lung cancer and cutaneous leishmaniasis are critical diseases with a relatively higher incidence in developing countries. In this research, the activity of Carissa macrocarpa leaf hydromethanolic extract and its solvent-fractions (n-hexane, EtOAc, n-butanol, and MeOH) against the lung adenocarcinoma cell line (A549) and Leishmania major was investigated. The MeOH fraction exhibited higher cytotoxic activity (IC50 1.57 ± 0.04 μg/mL) than the standard drug, etoposide (IC50 50.8 ± 3.16 μg/mL). The anti-L. major results revealed strong growth inhibitory effects of the EtOAc fraction against L. major promastigotes (IC50 27.52 ± 0.7 μg/mL) and axenic amastigotes (29.33 ± 4.86% growth inhibition at 100 μg/mL), while the butanol fraction exerted moderate activity against promastigotes (IC50 73.17 ± 1.62), as compared with miltefosine against promastigotes (IC50 6.39 ± 0.29 μg/mL) and sodium stibogluconate against axenic amastigotes (IC50 22.45 ± 2.22 μg/mL). A total of 102 compounds were tentatively identified using UPLC-ESI-MS/MS analysis of the total extract and its fractions. The MeOH fraction was found to contain several flavonoids and flavan-3-ol derivatives with known cytotoxic properties, whereas the EtOAc fractions contained triterpene, hydroxycinnamoyl, sterol, and flavanol derivatives with known antileishmanial activity. Molecular docking of various polyphenolics of the MeOH fraction with HDAC6 and PDK3 enzymes demonstrates high binding affinity of the epicatechin 3-O-β-D-glucopyranoside and catechin-7-O-β-D-glucopyranoside toward HDAC6, and procyanidin C2, procyanidin B5 toward PDK3. These results are promising and encourage the pursuit of preclinical research using C. macrocarpa's MeOH fraction as anti-lung cancer and the EtOAc fraction as an anti-L. major drug candidates. [ABSTRACT FROM AUTHOR]

The objectives of this study are to investigate the cytotoxic effect of different Citrullus colocynthis extracts on breast and lung cancer cell lines using flow cytometry to gain mechanistic insights. C. colocynthis was extracted sequentially using the Soxhlet method. We first tested the plant extracts' cytotoxicity on non-malignant L929 cells and cancerous breast (MCF-7) and lung (A549) cell lines. We observed that the IC50 of the methanol extract on the viability of MCF-7 and A549 cell lines was 81.08 µg/mL and 17.84 µg/mL, respectively, using the MTT assay. The aqueous and methanol extracts were less toxic when tested against the non-cancerous L929 cell line, with IC50 values of 235.48 µg/mL and 222.29 µg/mL, respectively. Then, using flow cytometry, we investigated the underlying molecular pathways with Annexin-V, Anti-Bcl-2, Caspase-3, and DNA fragmentation (TUNEL) assays. Flow cytometric and molecular marker analyses revealed that the methanol extract activated caspase-3 and inhibited Bcl-2 protein, causing early and late apoptosis, as well as cell death via DNA damage in breast and lung cancer cells. These findings indicate that the methanol extract of C. colocynthis is cytotoxic to breast and lung cancer cell lines. The total phenolic and flavonoid content analysis results showed the methanolic extract of C. colocynthis has a concentration of 326.25 μg GAE/g dwt and 274.61 μg QE/g dwt, respectively. GC-MS analysis of the methanol extract revealed phytochemicals relevant to its cytotoxicity. [ABSTRACT FROM AUTHOR]

The objectives of this research were to carry out GC–MS and LC–MS-based phytochemical profiling of Barleria hochstetteri, as well as flow cytometry-based mechanistic investigations of the cytotoxic effect of its extracts against breast and lung cancer cell lines. This preclinical in vitro study was carried out in Saudi Arabia and India, from 11 August to 15 January 2022. Barleria hochstetteri was sequentially extracted using the Soxhlet extraction technique. Utilizing LC–MS and GC–MS methods, the phytochemical profiling was performed. Additionally, the total phenolic compounds and flavonoids were quantified in the plant extract using spectrophotometric techniques. In this study, we first examined the cytotoxicity of the plant extract on non-malignant L929 cells and on the carcinogenic MCF-7 and A549 cell lines. Then, we studied the underlying molecular pathways by means of Anti-Bcl-2, caspase-3, and DNA fragmentation (TUNEL) assays, using flow cytometry. The results revealed phenolic compounds and flavonoids to be the two major components in the methanolic extract of B. hochstetteri, with concentrations of 3210 µg GAE/g dwt and 1863 µg QE/g dwt, respectively. Results from GC–MS and LC–MS analyses revealed the presence of bioactive phytochemicals with known cytotoxicity. From the MTT assay on cell viability, the IC50 of the methanol extract for the MCF-7 and A549 cell lines were 219.67 and 144.30 µg/mL, respectively. With IC50 values of 324.24 and 266.66 µg/mL, respectively, the aqueous and methanol extracts were less toxic when tested against the non-cancerous L929 cell line. The extract caused early and late apoptosis in the tested breast and lung cancer cells by activating caspase-3 and inhibiting Bcl-2 protein, and it also caused cell death via DNA damage, based on flow cytometric and molecular marker analyses. These findings indicate that the methanol extract of B. hochstetteri was cytotoxic on breast cancer and lung cancer cell lines. To uncover cancer-fighting chemicals, there is a need for further research on B. hochstetteri, as it is a promising source of anti-cancer chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]

The ethyl acetate and dichloromethane-soluble fractions, from a soft coral Sarcophyton trocheliophorum total methanolic extract, exhibited significant anti-leishmanial and cytotoxic activities. These active fractions yielded a new cembranoid diterpene (1), two known analogues [sarcotrocheliol (2) and sarcophine (3)], and two sterols [(24S)-24-methylcholesterol (4) and gorgosterol (5)]. The structure of the new diterpene (1) was determined via a detailed analysis of its spectroscopic data. Compounds 3 and 5 demonstrated noticeable cytotoxicity on A549 (IC50 17.4 ± 1.9 µg/ml) and HepG2 (IC50 17.7 ± 1.5 µg/ml) cell lines, respectively. None of the isolates 1‒5 showed detectable anti-leishmanial activity (IC50 >100 µg/ml). [ABSTRACT FROM AUTHOR]

• The Agavaceae species extracts had promising cytotoxicity against some cancer cells. • Some fractions from P. tuberosa, Y. filamentosa and F. Watsoniana had strong cytotoxicity. • Cytotoxicity shown by extracts may be related to steroidal saponins present. Among the plants which are determined to be a promising source of anticarcenogenic agents are members of Agavaceae family which are common in tropical and subtropical regions such as Egypt. In this study, cytotoxic activity were assessed for the methanolic extracts and fractions from five members of Agavaceae family: Sansevieria cylindrica Bojer., Polianthes tuberosa L., Sansevieria trifasciata Prain., Yucca filamentosa L. and Furcraea watsoniana Hort. against MCF-7 (breast), HepG-2 (hepatoma), and Caco-2 (colon) cancer cell lines by MTT method. The n -hexane fraction of P. tuberosa leaves extract demonstrated strong cytotoxic potential against all three cancer cell lines (CC 50 <20 µg/ml). The ethyl acetate fractions of Y. filamentosa and F. watsoniana leaves significantly inhibited proliferation of hepatocellular HepG-2 (CC 50 = 6.21 µg/ml and 19.07 µg/ml, respectively) and intestinal epithelium Caco-2 carcinoma cells (CC 50 = 18.86 µg/ml and 23.25 µg/ml, respectively). Presumably, the cytotoxic activity exhibited by n -hexane fraction of P. tuberosa , ethyl acetate fractions of Y. filamentosa and F. watsoniana may be related to the steroidal saponins that are present in these samples. [ABSTRACT FROM AUTHOR]

Investigation on tannins having antitumor properties led to the isolation of two new C -glycosidic ellagitannins (1 and 2) along with seven known ellagitannins (3 – 9) and a related polyphenolic constituent (10) from Lawsonia inermis leaves. Our intensive HRESIMS, 1D and 2D NMR, and ECD spectroscopic studies of new tannins have shown that one (1) has a monomer structure of C -glycosidic tannin, and the other (2) has a dimeric structure of 2,3- O -hexahydroxydiphenoyl glucopyranose and a C -glycosidic tannin. Among the known compounds, one (3) is a C -glycosidic tannin that was isolated first of all from nature, five were C -glycosidic tannins, vescalagin (4), 1- O -methylvescalagin (5), castalagin (6), stachyurin (7), and casuarinin (8), and one was an O- glycosidic ellagitannin, tellimagrandin II (9). The remaining phenolic constituent from the leaves was identified as valoneic acid dilactone (10). The ellagitannins 1 , and 3 – 9 demonstrated noticeable cytotoxicity on human oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9–22), and lower effects on human oral normal cells (HGF, HPC, and HPLF). Tellimagrandin II (9) had the highest tumor-specific cytotoxicity, and also cleaved poly (ADP-ribose) polymerase 1 in HSC-2 cells. These findings showed that L. inermis ellagitannins may be a candidate for the production of anti-oral cancer materials. [Display omitted] • Two new (1 and 2), a first isolated from nature (3), and six knowns (4 – 9) ellagitannins, and a related phenolic (10) were isolated from leaves of L. inermis. • The ellagitannins (1 , 3 – 9) exhibited higher cytotoxicity against human oral cancer cell lines (HSC-2, HSC-4, and Ca9–22) than against human normal oral cells (HGF, HPC, and HPLF). • Tellimagrandin II (9) induced cleavage of PARP1 in HSC-2 cells. [ABSTRACT FROM AUTHOR]

The methanolic extract and its sub-extracts (viz , n –hexane, DCM, EtOAc and MeOH) of the soft coral Sarcophyton acutum were evaluated as anti- Leishmania major and as anticancer (against the HepG2, MCF-7, and A549 cell lines) using the MTT assay. Six polyhydroxy sterols (1–6) were isolated from the most active cytotoxic and anti-leishmanial EtOAc-soluble fraction. Their structures were established as two new polyhydroxy sterols, acutumosterols A (1) and B (2), and four known structural analogues (3 – 6) by intensive spectroscopic analyses, and by comparison with data of related compounds. Compound 4 exerted noticeable cytotoxicity against HepG2 cell line (IC 50 17.2 ± 1.5 μg/mL), while the other pure isolates showed weak to moderate cytotoxicity (24.8 ± 2.8–57.2 ± 5.2). The results were discussed in relation to the structural features of these closely related sterols. Unlabelled Image • The anti- Leishmania major and cytotoxic activities (against HepG2, MCF-7, and A549 cell lines) of the Red Sea soft coral Sarcophyton acutum were evaluated. • Two new, acutumosterols A (1) and B (2), and four known (3 – 6) polyhydroxy sterols were isolated from the most active ethyl acetate fraction. • Cytotoxicity and anti- L. major activities of the pure isolates (1 – 6) were evaluated. [ABSTRACT FROM AUTHOR]