Biotechnological approaches to the production of plant-derived promising anticancer agents: An update and overview

Li, Changxing; Galani, Saddia; Hassan, Faiz‐ul; Rashid, Zubia; Naveed, Muhammad; Fang, Daidong; Ashraf, Asma; Wang, Qi; Arif, Afsheen; Saeed, Muhammad; Chishti, Arif Ali; Li, Jianhua

doi:10.1016/j.biopha.2020.110918

Cited by 32 publications

(19 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secondary metabolites, demonstrating a diverse set of properties in the plant (influencing its development, protection against the adverse effects of external factors, etc.) may also show an extremely important effect from the human point of view, such as anti‐cancer, anti‐bacterial or anti‐viral properties [36–41] . Since these compounds are synthesized in the course of numerous and often complex biochemical transformations, the possibility of modulation of these processes is the focus of many scientists.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Accumulation of Betulinic Acid in Transgenic Hairy Roots of Senna obtusifolia Growing in the Sprinkle Bioreactor and Evaluation of Their Biological Properties in Various Biological Models

Kowalczyk

Sitarek

Toma

et al. 2021

Chemistry & Biodiversity

View full text Add to dashboard Cite

Betulinic acid, which is found in transgenic roots of Senna obtusifolia (L.) H.S.Irwin & Barneby, is a pentacyclic triterpene with distinctive pharmacological activities. In this study, we report the differences in the content of betulinic acid and selected anthraquinones in transgenic S. obtusifolia hairy roots with overexpression of the PgSS1 gene (SOPSS2 line) and in transformed hairy roots without this genetic construct (SOA41 line). Both hairy root lines grew in 10 L sprinkle bioreactor. Additionally, the extracts obtained from this plant material were used for biological tests. Our results demonstrated that the SOPSS2 hairy root cultures from the bioreactor showed an increase in the content of betulinic acid (38.125 mg/g DW), compared to the SOA41 hairy root line (4.213 mg/g DW). Biological studies have shown a cytotoxic and antiproliferative effect on U‐87MG glioblastoma cells, and altering the level of apoptotic proteins (Bax, p53, Puma and Noxa). Antimicrobial properties were demonstrated for both tested extracts, with a stronger effect of SOPSS2 extract. Moreover, both extracts showed moderate antiviral properties on norovirus surrogates.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhanced Accumulation of Betulinic Acid in Transgenic Hairy Roots of Senna obtusifolia Growing in the Sprinkle Bioreactor and Evaluation of Their Biological Properties in Various Biological Models

Kowalczyk

Sitarek

Toma

et al. 2021

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

“…However, extensive metabolic cross talks and shuttling of about 35 intermediates synthesized via 30 enzymatic reactions in four different types of tissue and five different sub-cellular compartments have prevented the development of commercially interesting biotechnological production methods [ 117 ]. Hopefully a breakthrough can afford a feasible method for kg scale production of vinca alkaloids [ 115 , 118 ].…”

Section: Cancer Diseasesmentioning

confidence: 99%

Natural Products That Changed Society

Christensen

2021

Biomedicines

View full text Add to dashboard Cite

Until the end of the 19th century all drugs were natural products or minerals. During the 19th century chemists succeeded in isolating pure natural products such as quinine, morphine, codeine and other compounds with beneficial effects. Pure compounds enabled accurate dosing to achieve serum levels within the pharmacological window and reproducible clinical effects. During the 20th and the 21st century synthetic compounds became the major source of drugs. In spite of the impressive results achieved within the art of synthetic chemistry, natural products or modified natural products still constitute almost half of drugs used for treatment of cancer and diseases like malaria, onchocerciasis and lymphatic filariasis caused by parasites. A turning point in the fight against the devastating burden of malaria was obtained in the 17th century by the discovery that bark from trees belonging to the genus Cinchona could be used for treatment with varying success. However isolation and use of the active principle, quinine, in 1820, afforded a breakthrough in the treatment. In the 20th century the synthetic drug chloroquine severely reduced the burden of malaria. However, resistance made this drug obsolete. Subsequently artemisinin isolated from traditional Chinese medicine turned out to be an efficient antimalarial drug overcoming the problem of chloroquine resistance for a while. The use of synthetic analogues such as chloroquine or semisynthetic drugs such as artemether or artesunate further improved the possibilities for healing malaria. Onchocerciasis (river blindness) made life in large parts of Africa and South America miserable. The discovery of the healing effects of the macrocyclic lactone ivermectin enabled control and partly elimination of the disease by annual mass distribution of the drug. Also in the case of ivermectin improved semisynthetic derivatives have found their way into the clinic. Ivermectin also is an efficient drug for treatment of lymphatic filariasis. The serendipitous discovery of the ability of the spindle toxins to control the growth of fast proliferating cancer cells armed physicians with a new efficient tool for treatment of some cancer diseases. These possibilities have been elaborated through preparation of semisynthetic analogues. Today vincristine and vinblastine and semisynthetic analogues are powerful weapons against cancer diseases.

show abstract

“…Natural products derived from plant specialized metabolism are highly demanded due to their effectiveness against a wide range of diseases, including taxanes to treat cancer (Changxing et al, 2020), tannins and flavonoids to treat diabetes (Mtewa et al, 2021) and flavonoids to treat hepatic alterations (Bachar et al, 2020), among others. However, both the low concentrations of specialized metabolites in their natural source and the overharvesting of wild plants which have left several species endangered are impediments to meet this increasing demand (Georgiev et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The Epigenetic Regulation in Plant Specialized Metabolism: DNA Methylation Limits Paclitaxel in vitro Biotechnological Production

et al. 2022

View full text Add to dashboard Cite

Environmental conditions are key factors in the modulation of the epigenetic mechanisms regulating gene expression in plants. Specifically, the maintenance of cell cultures in optimal in vitro conditions alters methylation patterns and, consequently, their genetic transcription and metabolism. Paclitaxel production in Taxus x media cell cultures is reduced during its maintenance in in vitro conditions, compromising the biotechnological production of this valuable anticancer agent. To understand how DNA methylation influences taxane production, the promoters of three genes (GGPPS, TXS, and DBTNBT) involved in taxane biosynthesis have been studied, comparing the methylation patterns between a new line and one of ~14 years old. Our work revealed that while the central promoter of the GGPPS gene is protected from cytosine methylation accumulation, TXS and DBTNBT promoters accumulate methylation at different levels. The DBTNBT promoter of the old line is the most affected, showing a 200 bp regulatory region where all the cytosines were methylated. This evidence the existence of specific epigenetic regulatory mechanisms affecting the last steps of the pathway, such as the DBTNBT promoter. Interestingly, the GGPPS promoter, a regulatory sequence of a non-specific taxane biosynthetic gene, was not affected by this mechanism. In addition, the relationship between the detected methylation points and the predicted transcription factor binding sites (TFBS) showed that the action of TFs would be compromised in the old line, giving a further explanation for the production reduction in in vitro cell cultures. This knowledge could help in designing novel strategies to enhance the biotechnological production of taxanes over time.

show abstract

Biotechnological approaches to the production of plant-derived promising anticancer agents: An update and overview

Cited by 32 publications

References 126 publications

Enhanced Accumulation of Betulinic Acid in Transgenic Hairy Roots of Senna obtusifolia Growing in the Sprinkle Bioreactor and Evaluation of Their Biological Properties in Various Biological Models

Enhanced Accumulation of Betulinic Acid in Transgenic Hairy Roots of Senna obtusifolia Growing in the Sprinkle Bioreactor and Evaluation of Their Biological Properties in Various Biological Models

Natural Products That Changed Society

The Epigenetic Regulation in Plant Specialized Metabolism: DNA Methylation Limits Paclitaxel in vitro Biotechnological Production

Contact Info

Product

Resources

About