Cytotoxic Bufadienolides from the Leaves of <i>Melianthus major</i>

Bedane, Kibrom Gebreheiwot; Brieger, Lukas; Strohmann, Carsten; Seo, Ean‐Jeong; Efferth, Thomas; Spiteller, Michael

doi:10.1021/acs.jnatprod.0c00060

Cited by 10 publications

(4 citation statements)

References 22 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The advent of the angiotensin-converting enzyme (ACE) inhibitors replaced the therapeutic use of cardiac glycosides, but in the case of nonresponsiveness to ACE inhibition, cardiac glycosides are still very helpful, if blood serum levels are closely monitored to avoid intoxication [ 6 , 7 , 8 , 9 , 10 ]. Cardiac glycosides also exert profound anticancer activity in vitro and in vivo [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Oleandrin was found to downregulate the DNA damage repair protein Rad51 [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Modes of Action of an Aqueous Nerium oleander Extract in Cancer Cells In Vitro and In Vivo

et al. 2023

Self Cite

View full text Add to dashboard Cite

Cancer drug resistance remains a major obstacle in clinical oncology. As most anticancer drugs are of natural origin, we investigated the anticancer potential of a standardized cold-water leaf extract from Nerium oleander L., termed Breastin. The phytochemical characterization by nuclear magnetic resonance spectroscopy (NMR) and low- and high-resolution mass spectrometry revealed several monoglycosidic cardenolides as major constituents (adynerin, neritaloside, odoroside A, odoroside H, oleandrin, and vanderoside). Breastin inhibited the growth of 14 cell lines from hematopoietic tumors and 5 of 6 carcinomas. Remarkably, the cellular responsiveness of odoroside H and neritaloside was not correlated with all other classical drug resistance mechanisms, i.e., ATP-binding cassette transporters (ABCB1, ABCB5, ABCC1, ABCG2), oncogenes (EGFR, RAS), tumor suppressors (TP53, WT1), and others (GSTP1, HSP90, proliferation rate), in 59 tumor cell lines of the National Cancer Institute (NCI, USA), indicating that Breastin may indeed bypass drug resistance. COMPARE analyses with 153 anticancer agents in 74 tumor cell lines of the Oncotest panel revealed frequent correlations of Breastin with mitosis-inhibiting drugs. Using tubulin-GFP-transfected U2OS cells and confocal microscopy, it was found that the microtubule-disturbing effect of Breastin was comparable to that of the tubulin-depolymerizing drug paclitaxel. This result was verified by a tubulin polymerization assay in vitro and molecular docking in silico. Proteome profiling of 3171 proteins in the NCI panel revealed protein subsets whose expression significantly correlated with cellular responsiveness to odoroside H and neritaloside, indicating that protein expression profiles can be identified to predict the sensitivity or resistance of tumor cells to Breastin constituents. Breastin moderately inhibited breast cancer xenograft tumors in vivo. Remarkably, in contrast to what was observed with paclitaxel monotherapy, the combination of paclitaxel and Breastin prevented tumor relapse, indicating Breastin’s potential for drug combination regimens.

show abstract

Section: Introductionmentioning

confidence: 99%

Molecular Modes of Action of an Aqueous Nerium oleander Extract in Cancer Cells In Vitro and In Vivo

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…8 Furthermore, other bufadienolides have been reported to be cytotoxic against various cancer cell lines. 19 Compounds 1−8, 3-C-β-D-glucopyranosyl-2,4,6,4′-tetrahydroxybenzophenone, and ellagic acid-4-O-β-D-xylopyranoside were tested for antibacterial activity against E. coli DSM 1116, M. smegmatis DSM ATCC 700084, S. aureus DSM 346, and B. subtilis DSM 10. Compound 8 showed weak activity against E. coli with an MIC value of 52.4 μM, which is about the same potency value as reported previously (MIC of 36.7 μM against another E. coli strain).…”

Section: ■ Results and Discussionmentioning

confidence: 95%

“…Compound 4 has been reported previously to be cytotoxic against the KB3.1 cell line . Furthermore, other bufadienolides have been reported to be cytotoxic against various cancer cell lines …”

Section: Resultsmentioning

confidence: 99%

Cytotoxic Compounds from the Stem Bark of Two subsp. of Bersama abyssinica

et al. 2021

Self Cite

View full text Add to dashboard Cite

Three new bufadienolides, namely, paulliniogenin A (1), paulliniogenin B (2), and 16β-formyloxybersamagenin 1,3,5-orthoacetate (3), together with two known bufadienolides and six known phenolic substances, were isolated from the stem bark of Bersama abyssinica subsp. abyssinica and B. abyssinica subsp. paullinioides. The structures of the compounds were elucidated based on their NMR and HRMS data analyses. The relative configurations were defined by single-crystal X-ray crystallography and NOESY correlations. Cytotoxicity against the L929 and KB3.1 cancer cell lines of the isolated compounds was investigated using an MTT assay. Paulliniogenin A (1) and 16β-hydroxybersamagenin-1,3,5-orthoacetate (4) showed cytotoxicity against the KB3.1 cell line with IC50 values of 1.4 ± 0.77 and 1.6 ± 0.81 μM, respectively. Moreover, paulliniogenin A (1) and paulliniogenin B (2) demonstrated weak activity against Staphylococcus aureus.

show abstract

“…and Avé-Lall Corms Chloroform Hypoxoside ( 19 ) Inhibits the growth of colon adenocarcinoma (HT-29), human cervical cancer cells (Hela) and breast adenocarcinoma (MCF7) cells causing DNA cell cycle arrest at the late G1 and/or early S phase [ 106 ] 17 Knowltonia capensis (L.) Huth * * * * * 18 Merwilla plumbea (Lindl.) Speta * * * * * 19 Melianthus major L Leaves Petroleum ether, chloroform, ethyl acetate and methanol Bufadienolide ( 20 ) and 2β-acetoxy-3,5-di-O-acetylhellebrigenin ( 21 ) Cytotoxicity towards human epithelial larynx carcinoma (Hep 2) and breast cancer (MCF-7) cell lines [ 107 , 108 ] 20 Pittosporum viridiflorum Sims Leaves and bark Acetone, methanol Pittoviridoside ( 22 ) Inhibits the growth of breast MCF-7, colorectal Caco-2, lung A549, cervical Hela and ovarian cancer A2780 cells [ 78 , 80 ] 21 ...…”

Section: Resultsmentioning

confidence: 99%

Plants Used for the Traditional Management of Cancer in the Eastern Cape Province of South Africa: A Review of Ethnobotanical Surveys, Ethnopharmacological Studies and Active Phytochemicals

Sagbo

Otang-Mbeng

2021

Molecules

View full text Add to dashboard Cite

Cancer occurrence is rapidly increasing all over the world, including in developing countries. The current trend in cancer management requires the use of herbal remedies since the majority of anticancer drugs are known to be costly, with unwanted side effects. In the Eastern Cape province, the use of medicinal plants for cancer management has been climbing steadily over the past two decades due to their cultural belief, low cost, efficacy, and safety claims. With the aim of identifying some potential anticancer plants for probable drug development, this study was undertaken to review plants reported by ethnobotanical surveys in the Eastern Cape province of South Africa for the traditional management of cancer. Information regarding plants used for cancer management in the Eastern Cape province was obtained from multidisciplinary databases and ethnobotanical books. About 24 plant species belonging to twenty families have been reported to be used for the traditional management of cancer in the Eastern Cape province. Among the anticancer plant species, only 16 species have been explored scientifically for their anticancer activities. This review authenticated the use of anticancer plant species in the Eastern Cape province and, therefore, identified several promising unexplored species for further scientific evaluation.

show abstract

Cytotoxic Bufadienolides from the Leaves of Melianthus major

Cited by 10 publications

References 22 publications

Molecular Modes of Action of an Aqueous Nerium oleander Extract in Cancer Cells In Vitro and In Vivo

Molecular Modes of Action of an Aqueous Nerium oleander Extract in Cancer Cells In Vitro and In Vivo

Cytotoxic Compounds from the Stem Bark of Two subsp. of Bersama abyssinica

Plants Used for the Traditional Management of Cancer in the Eastern Cape Province of South Africa: A Review of Ethnobotanical Surveys, Ethnopharmacological Studies and Active Phytochemicals

Contact Info

Product

Resources

About