Effect of ganoderic acid on proliferation pathways of leukemic T lymphocyte (JURKAT cells)

• Grant number: 19/00482-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2019
• End date: December 31, 2020
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Renata Gorjao
• Grantee: Ilana Souza Correa
• Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil

Abstract

Several studies have shown promising effects of compounds present in the Ganoderma lucidum extract on tumor cell growth. However, mechanisms controlled by these compounds are not yet established. The aim of this study is to evaluate the effects of different concentrations of ganoderic acid on intracellular signaling pathways involved in the proliferation of JURKAT cells (Leukemic T lymphocyte lineage). Initially, Jurkat cells will be grown in the presence and absence of 0 to 100 µg/mL of ganoderic acid for 24 and 48 hours. In parallel, human lymphocytes obtained from healthy volunteers without leukemia will be treated under the same conditions. Afterwards, the following parameters will be evaluated: integrity of cell membrane, DNA fragmentation and externalization of phosphatidylserine by flow cytometry to analyze the toxicity of the compound; cellular proliferative capacity by incorporation of BRDU; expression of total proteins as well as the phosphorylated forms of p42/44, Akt (ser 473), Jak1 (tyr 980), PKC-beta and zeta; mRNA expression of the anti-apoptotic genes bcl-2, bcl-xL, c-myc and apoptotic bad, bax, p53 and bid. We believe that if the compounds isolated from Ganoderma lucidum are able to modulate the pathways involved in cellular growth in addition to induction of apoptosis pathways, these natural products can be used as an important antitumor compound.