Abbas Khojasteh

All Publications

• A novel therapeutic strategy using a single non-toxic agent that produces consistent long-term control of orthotopic experimental glioblastomas Khojasteh, A., Pisani, L., Kiebish, M., Cao, T., Nagpal, S., Nastke, M., Adamson, P., Beinat, C., Gesta, S., Hurd, R., Spielman, D., Recht, L. OXFORD UNIV PRESS INC. 2025: v452-v453

  View details for DOI 10.1093/neuonc/noaf201.1795

  View details for Web of Science ID 001613221000039

• Reversal of the Warburg Effect with BPM31510 treatment in a quinone deficient C6 Glioma resulting in efficacy Kiebish, M. A., Khojasteh, A., Stopka, S., Aristizabal-Henao, J. J., Nagpal, S., Ghiglieri, L., Kendirli, M., Nastke, M., Gesta, S., Narain, N. R., Modur, V., Recht, L. AMER ASSOC CANCER RESEARCH. 2025

  View details for DOI 10.1158/1538-7445.AM2025-1527

  View details for Web of Science ID 001499827502424

• Monitoring of cancer ferroptosis with [18F]hGTS13, a system xc- specific radiotracer. Theranostics Moses, A., Malek, R., Kendirli, M. T., Cheung, P., Landry, M., Herrera-Barrera, M., Khojasteh, A., Granucci, M., Bukhari, S. A., Hooper, J. E., Hayden-Gephart, M., Dixon, S. J., Recht, L. D., Beinat, C. 2025; 15 (3): 836-849

  Abstract

  Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, characterized by resistance to conventional therapies and poor survival. Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has recently emerged as a promising therapeutic target for GBM treatment. However, there are currently no non-invasive imaging techniques to monitor the engagement of pro-ferroptotic compounds with their respective targets, or to monitor the efficacy of ferroptosis-based therapies. System xc-, an important player in cellular redox homeostasis, plays a critical role in ferroptosis by mediating the exchange of cystine for glutamate, thus regulating the availability of cysteine, a crucial precursor for glutathione synthesis, and influencing the cellular antioxidant defense system. We have recently reported the development and validation of [18F]hGTS13, a radiopharmaceutical specific for system xc-. Methods: In the current work, we characterized the sensitivity of various cell lines to pro-ferroptotic compounds and evaluated the ability of [18F]hGTS13 to distinguish between sensitive and resistant cell lines and monitor changes in response to ferroptosis-inducing investigational compounds. We then associated changes in [18F]hGTS13 uptake with cellular glutathione content. Furthermore, we evaluated [18F]hGTS13 uptake in a rat model of glioma, both before and after treatment with imidazole ketone erastin (IKE), a pro-ferroptotic inhibitor of system xc- activity. Results: Treatment with erastin2, a system xc- inhibitor, significantly decreased [18F]hGTS13 uptake and cellular glutathione content in vitro. Dynamic PET/CT imaging of C6 glioma-bearing rats with [18F]hGTS13 revealed high and sustained uptake within the intracranial glioma and this uptake was decreased upon pre-treatment with IKE. Conclusion: In summary, [18F]hGTS13 represents a promising tool to distinguish cell types that demonstrate sensitivity or resistance to ferroptosis-inducing therapies that target system xc-, and monitor the engagement of these drugs.

  View details for DOI 10.7150/thno.101882

  View details for PubMedID 39776801

  View details for PubMedCentralID PMC11700874

• OPTIMIZING BRAIN CANCER THERAPY: BALANCING TUMOR ERADICATION AND NORMAL TISSUE PRESERVATION WITH BPM31510 Khojasteh, A., Kendirli, M., Narain, N., Nagpal, S., Nastke, M., Gesta, S., Recht, L. OXFORD UNIV PRESS INC. 2024

  View details for DOI 10.1093/neuonc/noae165.0498

  View details for Web of Science ID 001362575700015

• IMPROVED ANTI-GLIOBLASTOMA EFFICACY BY BRG399, A NOVEL ORAL MICROTUBULE BINDING AGENT Kendirli, M., Nastke, M., Aristizabal-Henao, J., Khojasteh, A., Kiebish, M., Chimmanamada, D., Vishnudas, V., Recht, L., Gesta, S. OXFORD UNIV PRESS INC. 2024

  View details for DOI 10.1093/neuonc/noae165.0499

  View details for Web of Science ID 001362575500007

• Effect of Polyploidy Induction on Natural Metabolite Production in Medicinal Plants BIOMOLECULES Madani, H., Escrich, A., Hosseini, B., Sanchez-Munoz, R., Khojasteh, A., Palazon, J. 2021; 11 (6)

  Abstract

  Polyploidy plays an important role in plant diversification and speciation. The ploidy level of plants is associated with morphological and biochemical characteristics, and its modification has been used as a strategy to alter the quantitative and qualitative patterns of secondary metabolite production in different medicinal plants. Polyploidization can be induced by many anti-mitotic agents, among which colchicine, oryzalin, and trifluralin are the most common. Other variables involved in the induction process include the culture media, explant types, and exposure times. Due to the effects of polyploidization on plant growth and development, chromosome doubling has been applied in plant breeding to increase the levels of target compounds and improve morphological characteristics. Prompted by the importance of herbal medicines and the increasing demand for drugs based on plant secondary metabolites, this review presents an overview of how polyploidy can be used to enhance metabolite production in medicinal plants.

  View details for DOI 10.3390/biom11060899

  View details for Web of Science ID 000665342900001

  View details for PubMedID 34204200

  View details for PubMedCentralID PMC8234191

• Powerful Plant Antioxidants: A New Biosustainable Approach to the Production of Rosmarinic Acid ANTIOXIDANTS Khojasteh, A., Mirjalili, M., Alcalde, M., Cusido, R. M., Eibl, R., Palazon, J. 2020; 9 (12)

  Abstract

  Modern lifestyle factors, such as physical inactivity, obesity, smoking, and exposure to environmental pollution, induce excessive generation of free radicals and reactive oxygen species (ROS) in the body. These by-products of oxygen metabolism play a key role in the development of various human diseases such as cancer, diabetes, heart failure, brain damage, muscle problems, premature aging, eye injuries, and a weakened immune system. Synthetic and natural antioxidants, which act as free radical scavengers, are widely used in the food and beverage industries. The toxicity and carcinogenic effects of some synthetic antioxidants have generated interest in natural alternatives, especially plant-derived polyphenols (e.g., phenolic acids, flavonoids, stilbenes, tannins, coumarins, lignins, lignans, quinines, curcuminoids, chalcones, and essential oil terpenoids). This review focuses on the well-known phenolic antioxidant rosmarinic acid (RA), an ester of caffeic acid and (R)-(+)-3-(3,4-dihydroxyphenyl) lactic acid, describing its wide distribution in thirty-nine plant families and the potential productivity of plant sources. A botanical and phytochemical description is provided of a new rich source of RA, Satureja khuzistanica Jamzad (Lamiaceae). Recently reported approaches to the biotechnological production of RA are summarized, highlighting the establishment of cell suspension cultures of S. khuzistanica as an RA chemical biofactory.

  View details for DOI 10.3390/antiox9121273

  View details for Web of Science ID 000601674000001

  View details for PubMedID 33327619

  View details for PubMedCentralID PMC7765155

• Genomic methylation in plant cell cultures: A barrier to the development of commercial long-term biofactories ENGINEERING IN LIFE SCIENCES Sanchez-Munoz, R., Moyano, E., Khojasteh, A., Bonfill, M., Cusido, R. M., Palazon, J. 2019; 19 (12): 872-879

  Abstract

  Plant cell biofactories offer great advantages for the production of plant compounds of interest, although certain limitations still need to be overcome before their maximum potential is reached. One obstacle is the gradual loss of secondary metabolite production during in vitro culture maintenance, which is an important impediment in the development of large-scale production systems. The relationship between in vitro maintenance and epigenetic changes has been demonstrated in several plant species; in particular, methylation levels have been found to increase in in vitro cultures over time. Higher DNA methylation levels have been correlated with a low yield of secondary metabolites in in vitro plant cell cultures. The longer the period of subculturing, the more methylated cytosines were found throughout the genome, and secondary metabolism decreased significantly. This review summarizes different studies on epigenetic changes during the maintenance of in vitro cell cultures and the insights they provide on the mechanisms involved. It concludes by looking at the perspectives for new approaches designed to avoid declines in metabolite production.

  View details for DOI 10.1002/elsc.201900024

  View details for Web of Science ID 000502733000005

  View details for PubMedID 32624979

  View details for PubMedCentralID PMC6999079

• Biotechnological production of ruscogenins in plant cell and organ cultures of <i>Ruscus aculeatus</i> PLANT PHYSIOLOGY AND BIOCHEMISTRY Khojasteh, A., Sanchez-Munoz, R., Moyano, E., Bonfill, M., Cusido, R. M., Eibl, R., Palazo, J. 2019; 141: 133-141

  Abstract

  Ruscus aculeatus is a threatened medicinal plant whose main bioactive components, the ruscogenins, have long been used in the treatment of hemorrhoids and varicose veins, but recently demonstrated activity against some types of cancer. Plant cell biofactories could constitute an alternative to the whole plant as a source of ruscogenins. In this pipeline, despite the in vitro recalcitrance of R. aculeatus, after many attempts we developed friable calli and derived plant cell suspensions, and their ruscogenin production was compared with that of organized in vitro plantlet and root-rhizome cultures. Root-rhizomes showed a higher capacity for biomass and ruscogenin production than the cell suspensions and the yields were greatly improved by elicitation with coronatine. Although ruscogenins accumulate in plants mainly in the root-rhizome, it was demonstrated that the aerial part could play an important role in their biosynthesis, as production was higher in the whole plant than in the root-rhizome cultures.

  View details for DOI 10.1016/j.plaphy.2019.05.029

  View details for Web of Science ID 000475997300013

  View details for PubMedID 31163340

• In Vitro Study of the Anticancer Effects of Biotechnological Extracts of the Endangered Plant Species Satureja Khuzistanica INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Khojasteh, A., Meton, I., Camino, S., Cusido, R. M., Eibl, R., Palazon, J. 2019; 20 (10)

  Abstract

  Many medicinal plant species are currently threatened in their natural habitats because of the growing demand for phytochemicals worldwide. A sustainable alternative for the production of bioactive plant compounds are plant biofactories based on cell cultures and organs. In addition, plant extracts from biofactories have significant advantages over those obtained from plants, since they are free of contamination by microorganisms, herbicides and pesticides, and they provide more stable levels of active ingredients. In this context, we report the establishment of Satureja khuzistanica cell cultures able to produce high amounts of rosmarinic acid (RA). The production of this phytopharmaceutical was increased when the cultures were elicited with coronatine and scaled up to a benchtop bioreactor. S. khuzistanica extracts enriched in RA were found to reduce the viability of cancer cell lines, increasing the sub-G0/G1 cell population and the activity of caspase-8 in MCF-7 cells, which suggest that S. khuzistanica extracts can induce apoptosis of MCF-7 cells through activation of the extrinsic pathway. In addition, our findings indicate that other compounds in S. khuzistanica extracts may act synergistically to potentiate the anticancer activity of RA.

  View details for DOI 10.3390/ijms20102400

  View details for Web of Science ID 000471001400031

  View details for PubMedID 31096565

  View details for PubMedCentralID PMC6566673

• <i>Taxus</i> Cell Cultures: An Effective Biotechnological Tool to Enhance and Gain New Biosynthetic Insights into Taxane Production BIOPROCESSING OF PLANT IN VITRO SYSTEMS Vidal-Limon, H., Sanchez-Munoz, R., Khojasteh, A., Moyano, E., Cusido, R. M., Palazon, J. edited by Pavlov, A., Bley, T. 2018: 295-316

  View details for DOI 10.1007/978-3-319-54600-1_5

  View details for Web of Science ID 000459809600011

• Methyl jasmonate enhanced production of rosmarinic acid in cell cultures of <i>Satureja khuzistanica</i> in a bioreactor ENGINEERING IN LIFE SCIENCES Khojasteh, A., Mirjalili, M., Palazon, J., Eibl, R., Cusido, R. M. 2016; 16 (8): 740-749

  View details for DOI 10.1002/elsc.201600064

  View details for Web of Science ID 000396913400007

• Plant Anti-cancer Agents and their Biotechnological Production in Plant Cell Biofactories CURRENT MEDICINAL CHEMISTRY Lalaleo, L., Khojasteh, A., Fattahi, M., Bonfill, M., Cusido, R. M., Palazon, J. 2016; 23 (39): 4418-4441

  Abstract

  Bioactive plant secondary metabolites have complex chemical structures, which are specific to each plant species/family, and accumulate in tiny amounts. The growing market demand for many phytochemicals can lead to the over-harvesting of medicinal plants in their natural habitat, endangering species in the process.An ongoing challenge for our society is therefore to develop a bio-sustainable production of phytochemicals, among other natural resources. Cancer is currently a major health problem, responsible for approximately 8.2 million deaths per year worldwide. We therefore focused this review on cancer therapeutic agents from plants and their biotechnological production.An extensive review of the literature shows that although a wide range of phytochemicals have demonstrated anti-proliferative activity in vitro, only a few examples of plant-based drugs are included in the Anatomical Therapeutic Chemical (ATC) classification as antineoplastic agents. These include vinca alkaloids and their derivatives (L01CA), podophyllotoxin derivatives (L01CB), and paclitaxel and its derivatives (L01CD), as well as camptothecin derivatives (L01XX). These compounds all have in common a complex chemical structure, a scarce distribution in nature, and a high added value. After describing the chemical structures, natural sources and biological activities of these anticancer compounds, we focus on the state of the art in their biotechnological production in plant cell biofactories.More in-depth studies are required on the biosynthesis of target plant metabolites and its regulation in order to increase their biotechnological production in plant cell factories and ultimately implement these biosustainable processes at an industrial level.

  View details for DOI 10.2174/0929867323666161024145715

  View details for Web of Science ID 000390648800002

  View details for PubMedID 27781948