Digitonin synergistically enhances the cytotoxicity of plant secondary metabolites in cancer cells

Phytomedicine ◽  
2012 ◽  
Vol 19 (14) ◽  
pp. 1307-1314 ◽  
Author(s):  
Safaa Yehia Eid ◽  
Mahmoud Zaki El-Readi ◽  
Michael Wink
Keyword(s):  
Secondary Metabolites ◽  
Cancer Cells ◽  
Plant Secondary Metabolites

scholarly journals Multiple Molecular Mechanisms to Overcome Multidrug Resistance in Cancer by Natural Secondary Metabolites

2021 ◽  
Vol 12 ◽  
Author(s):  
Mahmoud Zaki El-Readi ◽  
Ahmed M. Al-Abd ◽  
Mohammad A. Althubiti ◽  
Riyad A. Almaimani ◽  
Hiba Saeed Al-Amoodi ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Secondary Metabolites ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Plant Secondary Metabolites ◽  
Cell Growth Inhibition ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Drug Concentrations ◽  
Pharmaceutical Agents

Plant secondary metabolites (SMs) common natural occurrences and the significantly lower toxicities of many SM have led to the approaching development and use of these compounds as effective pharmaceutical agents; especially in cancer therapy. A combination of two or three of plant secondary metabolites together or of one SM with specific anticancer drugs, may synergistically decrease the doses needed, widen the chemotherapeutic window, mediate more effective cell growth inhibition, and avoid the side effects of high drug concentrations. In mixtures they can exert additive or even synergistic activities. Many SM can effectively increase the sensitivity of cancer cells to chemotherapy. In phytotherapy, secondary metabolites (SM) of medicinal plants can interact with single or multiple targets. The multi-molecular mechanisms of plant secondary metabolites to overcome multidrug resistance (MDR) are highlighted in this review. These mechanisms include interaction with membrane proteins such as P-glycoprotein (P-gp/MDR1); an ATP-binding cassette (ABC) transporter, nucleic acids (DNA, RNA), and induction of apoptosis. P-gp plays an important role in the development of MDR in cancer cells and is involved in potential chemotherapy failure. Therefore, the ingestion of dietary supplements, food or beverages containing secondary metabolites e.g., polyphenols or terpenoids may alter the bioavailability, therapeutic efficacy and safety of the drugs that are P-gp substrates.

Caffeoylquinic Acids with Potential Biological Activity from Plant In vitro Cultures as Alternative Sources of Valuable Natural Products

2020 ◽  
Vol 26 (24) ◽  
pp. 2817-2842
Author(s):  
Ewa Skała ◽  
Joanna Makowczyńska ◽  
Joanna Wieczfinska ◽  
Tomasz Kowalczyk ◽  
Przemysław Sitarek
Keyword(s):  
Secondary Metabolites ◽  
Cell Suspension ◽  
Plant Species ◽  
Plant Secondary Metabolites ◽  
Cell Suspension Cultures ◽  
In Vitro Cultures ◽  
Transformed Roots ◽  
Transgenic Roots ◽  
Plant In Vitro Cultures

Background: For a long time, the researchers have been looking for new efficient methods to enhance production and obtain valuable plant secondary metabolites, which would contribute to the protection of the natural environment through the preservation of various plant species, often rare and endangered. These possibilities offer plant in vitro cultures which can be performed under strictly-controlled conditions, regardless of the season or climate and environmental factors. Biotechnological methods are promising strategies for obtaining the valuable plant secondary metabolites with various classes of chemical compounds including caffeoylquinic acids (CQAs) and their derivatives. CQAs have been found in many plant species which are components in the daily diet and exhibit a wide spectrum of biological activities, including antioxidant, immunomodulatory, antihypertensive, analgesic, anti-inflammatory, hepato- and neuroprotective, anti-hyperglycemic, anticancer, antiviral and antimicrobial activities. They have also been found to offer protection against Alzheimer’s disease, and play a role in weight reduction and lipid metabolism control, as well as modulating the activity of glucose-6-phosphatase involved in glucose metabolism. Methods: This work presents the review of the recent advances in use in vitro cultures of various plant species for the alternative system to the production of CQAs and their derivatives. Production of the secondary metabolites in in vitro culture is usually performed with cell suspension or organ cultures, such as shoots and adventitious or transformed roots. To achieve high production of valuable secondary metabolites in in vitro cultures, the optimization of the culture condition is necessary with respect to both biomass accumulation and metabolite content. The optimization of the culture conditions can be achieved by choosing the type of medium, growth regulators or growth conditions, selection of high-productivity lines or culture period, supplementation of the culture medium with precursors or elicitor treatments. Cultivation for large-scale in bioreactors and genetic engineering: Agrobacterium rhizogenes transformation and expression improvement of transcriptional factor or genes involved in the secondary metabolite production pathway are also efficient strategies for enhancement of the valuable secondary metabolites. Results: Many studies have been reported to obtain highly productive plant in vitro cultures with respect to CQAs. Among these valuable secondary metabolites, the most abundant compound accumulated in in vitro cultures was 5-CQA (chlorogenic acid). Highly productive cultures with respect to this phenolic acid were Leonurus sibiricus AtPAP1 transgenic roots, Lonicera macranthoides and Eucomia ulmoides cell suspension cultures which accumulated above 20 mg g-1 DW 5-CQA. It is known that di- and triCQAs are less common in plants than monoCQAs, but it was also possible to obtain them by biotechnological methods. Conclusion: The results indicate that the various in vitro cultures of different plant species can be a profitable approach for the production of CQAs. In particular, an efficient production of these valuable compounds is possible by Lonicera macranthoides and Eucomia ulmoides cell suspension cultures, Leonurus sibiricus transformed roots and AtPAP1 transgenic roots, Echinacea angustifolia adventitious shoots, Rhaponticum carthamoides transformed plants, Lavandula viridis shoots, Sausera involucrata cell suspension and Cichorium intybus transformed roots.

Plant Secondary Metabolites in Cancer Chemotherapy: Where are We?

2012 ◽  
Vol 13 (5) ◽  
pp. 632-650 ◽  
Author(s):  
David M. Pereira ◽  
Patricia Valentao ◽  
Georgina Correia-da-Silva ◽  
Natercia Teixeira ◽  
Paula B. Andrade
Keyword(s):  
Secondary Metabolites ◽  
Cancer Chemotherapy ◽  
Plant Secondary Metabolites

Plant Extracts and their Secondary Metabolites as Modulators of Kinases

2020 ◽  
Vol 20 (12) ◽  
pp. 1093-1104 ◽  
Author(s):  
Muhammad Shoaib Ali Gill ◽  
Hammad Saleem ◽  
Nafees Ahemad
Keyword(s):  
Signal Transduction ◽  
Secondary Metabolites ◽  
Plant Extracts ◽  
Cell Biology ◽  
Kinase Inhibitor ◽  
Plant Secondary Metabolites ◽  
Biological Properties ◽  
Drug Candidate ◽  
New Chemical Entities ◽  
Natural Flora

Natural Products (NP), specifically from medicinal plants or herbs, have been extensively utilized to analyze the fundamental mechanisms of ultimate natural sciences as well as therapeutics. Isolation of secondary metabolites from these sources and their respective biological properties, along with their lower toxicities and cost-effectiveness, make them a significant research focus for drug discovery. In recent times, there has been a considerable focus on isolating new chemical entities from natural flora to meet the immense demand for kinase modulators, and also to overcome major unmet medical challenges in relation to signal transduction pathways. The signal transduction systems are amongst the foremost pathways involved in the maintenance of life and protein kinases play an imperative part in these signaling pathways. It is important to find a kinase inhibitor, as it can be used not only to study cell biology but can also be used as a drug candidate for cancer and metabolic disorders. A number of plant extracts and their isolated secondary metabolites such as flavonoids, phenolics, terpenoids, and alkaloids have exhibited activities against various kinases. In the current review, we have presented a brief overview of some important classes of plant secondary metabolites as kinase modulators. Moreover, a number of phytocompounds with kinase inhibition potential, isolated from different plant species, are also discussed.

scholarly journals Target screening of plant secondary metabolites in river waters by liquid chromatography coupled to high-resolution mass spectrometry (LC–HRMS)

2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Mulatu Yohannes Nanusha ◽  
Martin Krauss ◽  
Carina D. Schönsee ◽  
Barbara F. Günthardt ◽  
Thomas D. Bucheli ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Surface Waters ◽  
High Resolution Mass Spectrometry ◽  
Water Cycle ◽  
Endocrine Disrupting Chemicals ◽  
Plant Secondary Metabolites ◽  
Biologically Active ◽  
Plant Metabolites ◽  
River Waters ◽  
Target Screening

Abstract Background Substantial efforts have been made to monitor potentially hazardous anthropogenic contaminants in surface waters while for plant secondary metabolites (PSMs) almost no data on occurrence in the water cycle are available. These metabolites enter river waters through various pathways such as leaching, surface run-off and rain sewers or input of litter from vegetation and might add to the biological activity of the chemical mixture. To reduce this data gap, we conducted a LC–HRMS target screening in river waters from two different catchments for 150 plant metabolites which were selected from a larger database considering their expected abundance in the vegetation, their potential mobility, persistence and toxicity in the water cycle and commercial availability of standards. Results The screening revealed the presence of 12 out of 150 possibly toxic PSMs including coumarins (bergapten, scopoletin, fraxidin, esculetin and psoralen), a flavonoid (formononetin) and alkaloids (lycorine and narciclasine). The compounds narciclasine and lycorine were detected at concentrations up to 3 µg/L while esculetin and fraxidin occurred at concentrations above 1 µg/L. Nine compounds occurred at concentrations above 0.1 µg/L, the Threshold for Toxicological Concern (TTC) for non-genotoxic and non-endocrine disrupting chemicals in drinking water. Conclusions Our study provides an overview of potentially biologically active PSMs in surface waters and recommends their consideration in monitoring and risk assessment of water resources. This is currently hampered by a lack of effect data including toxicity to aquatic organisms, endocrine disruption and genotoxicity and demands for involvement of these compounds in biotesting.

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