Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells

Mohamed Elamir F. Hegazy, Sara Abdelfatah, Ahmed R. Hamed, Tarik A. Mohamed, Abdelsamed A. Elshamy, Ibrahim A. Saleh, Eman H. Reda, Nahla S. Abdel-Azim, Khaled A. Shams, Mahmoud Sakr, Yoshikazu Sugimoto, Paul W. Paré, Thomas Efferth

Research output: Contribution to journalArticle

Abstract

Background: The multidrug resistance (MDR) phenotype encounters a major challenge to the success of established chemotherapy in cancer patients. We hypothesized that cytotoxic medicinal plants with novel phytochemicals can overcome MDR and kill MDR-cells with similar efficacy as drug sensitive cells. Purpose: We evaluated plant extracts from an unexplored ecosystem in Egypt with unusual climate and nutrient conditions for their activity against sensitive and multidrug-resistant cancer cell lines. Material and methods/study design: Methylene chloride: methanol (1:1) and methanol: H 2 O (7:3) extracts of 40 plants were prepared resulting in a sum of 76 fraction containing compounds with varying polarity. The resazurin reduction assay was employed to evaluate the cytotoxicity of these extracts on five matched pairs of drug-sensitive and their drug-resistant cell lines. Flow cytometry and Western blotting was used to determine cell cycle analyses, apoptosis, and autophagy. Reactive oxygen species (ROS) were measured spectrophotometrically. Results: Extracts derived from Withania obtusifolia (WO), Jasonia candicans (JC), Centaurea lippii (CL), and Pulicaria undulata (PU) were the most active ones among 76 extracts from 40 Egyptian medicinal plants. They showed a significant reduction of cell viability on drug-sensitive CCRF-CEM leukemia cell line with IC 50 values less than 7 µg/ml. Low cross-resistance degrees were observed in multidrug-resistant CEM/ADR5000 cells towards CL (1.82-fold) and JC (6.09-fold). All other drug-resistant cell lines did not reveal cross-resistance to the four extracts. Further mechanistic assessment have been studied for these four extracts. Conclusion: The methylene chloride: methanol (1:1) fractions of WO, JC, CL, and PU are promising cytotoxic extracts that could be used to combat MDR cancer cells through different cell death pathways.

Original languageEnglish
Article number152771
JournalPhytomedicine
Volume59
DOIs
Publication statusPublished - 2019 Jun 1

Fingerprint

Plant Extracts
Drug Delivery Systems
Centaurea
Multiple Drug Resistance
Pulicaria
Withania
Methanol
Cell Line
Pharmaceutical Preparations
Methylene Chloride
Neoplasms
Medicinal Plants
Egypt
Autophagy
Phytochemicals
Climate
Ecosystem
Reactive Oxygen Species
Cell Survival
Cell Cycle

Keywords

  • Cytotoxicity
  • Egypt
  • Mode of action
  • Multidrug resistance
  • Wild medicinal plants

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

Cite this

Hegazy, M. E. F., Abdelfatah, S., Hamed, A. R., Mohamed, T. A., Elshamy, A. A., Saleh, I. A., ... Efferth, T. (2019). Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells. Phytomedicine, 59, [152771]. https://doi.org/10.1016/j.phymed.2018.11.031

Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells. / Hegazy, Mohamed Elamir F.; Abdelfatah, Sara; Hamed, Ahmed R.; Mohamed, Tarik A.; Elshamy, Abdelsamed A.; Saleh, Ibrahim A.; Reda, Eman H.; Abdel-Azim, Nahla S.; Shams, Khaled A.; Sakr, Mahmoud; Sugimoto, Yoshikazu; Paré, Paul W.; Efferth, Thomas.

In: Phytomedicine, Vol. 59, 152771, 01.06.2019.

Research output: Contribution to journalArticle

Hegazy, MEF, Abdelfatah, S, Hamed, AR, Mohamed, TA, Elshamy, AA, Saleh, IA, Reda, EH, Abdel-Azim, NS, Shams, KA, Sakr, M, Sugimoto, Y, Paré, PW & Efferth, T 2019, 'Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells', Phytomedicine, vol. 59, 152771. https://doi.org/10.1016/j.phymed.2018.11.031
Hegazy MEF, Abdelfatah S, Hamed AR, Mohamed TA, Elshamy AA, Saleh IA et al. Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells. Phytomedicine. 2019 Jun 1;59. 152771. https://doi.org/10.1016/j.phymed.2018.11.031
Hegazy, Mohamed Elamir F. ; Abdelfatah, Sara ; Hamed, Ahmed R. ; Mohamed, Tarik A. ; Elshamy, Abdelsamed A. ; Saleh, Ibrahim A. ; Reda, Eman H. ; Abdel-Azim, Nahla S. ; Shams, Khaled A. ; Sakr, Mahmoud ; Sugimoto, Yoshikazu ; Paré, Paul W. ; Efferth, Thomas. / Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells. In: Phytomedicine. 2019 ; Vol. 59.
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AU - Hamed, Ahmed R.

AU - Mohamed, Tarik A.

AU - Elshamy, Abdelsamed A.

AU - Saleh, Ibrahim A.

AU - Reda, Eman H.

AU - Abdel-Azim, Nahla S.

AU - Shams, Khaled A.

AU - Sakr, Mahmoud

AU - Sugimoto, Yoshikazu

AU - Paré, Paul W.

AU - Efferth, Thomas

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