Molecular Mechanisms Responsible for In Vitro Cytotoxic Attributes of Conyza bonariensis Extract against Lymphoblastic Leukaemia Jurkat Cells

Author:

Saleem Mohammad1,Schini-Kerth Valerie B2,Hussain Khalid1,Khalid Syed Haroon3,Asif Muhammad4,Alhosin Mahmoud5,Akhtar Muhammad Furqan6,Ahmad Bashir6,Raza Atif1,Mahrukh 1

Affiliation:

1. Punjab University College of Pharmacy, University of The Punjab Lahore , Pakistan

2. UMR 1260 INSERM Nanomédecine Régénérative, Faculté de Pharmacie,Université de Strasbourg, 74, route du Rhin - BP 60024, 67401 Illkirch, France

3. Faculty of Pharmaceutical Sciences, Government College University of Faisalabad, Pakistan

4. Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Punjab, Pakistan

5. Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia

6. Riphah Institute of Pharmaceutical Sciences, Riphah International University Lahore, Lahore 54000, Pakistan

Abstract

Background: Conyza bonariensis is known to have anti-cancer properties. Objective: The study investigated the in vitro pro-apoptotic properties of Conyza bonariensis (C. bonariensis) towards human lymphoblastic leukemia Jurkat cells. Methods: C. bonariensis are extracted with non-polar solvent by maceration. MTS cell viability assay was employed to determine the cytotoxic activity of the extract towards human leukemia Jurket cells and normal Peripheral Blood Mononuclear Cells (PBMCs) cells. The phytochemical composition of the extract was chemically characterized using HPLC. Flow cytometric studies (FACS) were conducted to explore the pro-apoptotic potential of the extract. Western blot studies were employed to identify the molecular targets involved in the induction of apoptosis. Results: The n-hexane extract showed selective cytotoxic activity towards Jurkat cells. FACS analysis indicated that the extract induced early and late apoptosis in Jurkat cells. Western blot studies revealed that the extract down-regulated the expression of DNMT1, SIRT1, and UHRF1 with a simultaneous up-regulation of the expression of p73 and caspases-3 proteins. HPLC characterization of the extract revealed the presence of phenolic compounds. Conclusion: Overall these findings demonstrate that the anticancer effects of a Conyza bonariensis extract towards human lymphoblastic leukemiais due to the modulation of the activity of multiple oncogenic and tumor suppressor proteins and that its phenolic content is involved are proposed to be responsible for these activities.

Publisher

Bentham Science Publishers Ltd.

Subject

Cancer Research,Pharmacology,Molecular Medicine

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