Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.

Autor: Dulay RM; Center for Tropical Mushroom Research and Development, Department of Biological Sciences, College of Science, Central Luzon State University, Science City of Muñoz, Nueva Ecija, Philippines.; Department of Biology, College of Science, De La Salle University, Manila, Philippines., Valdez BC; Department of Stem Cell Transplantation and Cellular Therapy, UT MD Anderson Cancer Center, Houston, Texas, United States of America., Li Y; Department of Stem Cell Transplantation and Cellular Therapy, UT MD Anderson Cancer Center, Houston, Texas, United States of America., Chakrabarti S; Department of Plant Pathology, University of Florida, Ft. Lauderdale Research and Education Center, Davie, Florida, United States of America., Dhillon B; Department of Plant Pathology, University of Florida, Ft. Lauderdale Research and Education Center, Davie, Florida, United States of America., Kalaw SP; Center for Tropical Mushroom Research and Development, Department of Biological Sciences, College of Science, Central Luzon State University, Science City of Muñoz, Nueva Ecija, Philippines., Reyes RG; Center for Tropical Mushroom Research and Development, Department of Biological Sciences, College of Science, Central Luzon State University, Science City of Muñoz, Nueva Ecija, Philippines., Cabrera EC; Department of Biology, College of Science, De La Salle University, Manila, Philippines.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 May 28; Vol. 16 (5), pp. e0252541. Date of Electronic Publication: 2021 May 28 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0252541
Abstrakt: Treatment of hematologic malignancies is a formidable challenge for hematologists and there is an urgent need to identify safe and efficacious agents either via synthesis in the laboratory or isolation from natural products. Here, we report the cytotoxicity of extracts from mushroom Gymnopilus purpureosquamulosus Høil (G. pps) and describe its molecular mechanisms. Using leukemia, lymphoma and multiple myeloma cell lines, 28-35 ppm G. pps extract inhibited cell proliferation by ~46-79%, which correlates with activation of apoptosis as indicated by increase in annexin V-positive cells (~5-8-fold), production of reactive oxygen species (~2-3-fold), cells in sub G0/G1 phase (~3-13-fold), caspase 3 enzymatic activity (~1.6-2.9-fold), DNA fragmentation, PARP1 cleavage and down-regulation of prosurvival proteins. Mitochondrial membrane potential decreased and leakage of pro-apoptotic factors to cytoplasm was observed, consistent with the activation of intrinsic apoptosis. Western blot analysis showed activation of the ASK1-MEK-SAPK/JNK and ASK1-P38 MAPK pathways possibly due to changes in the cellular redox status as suggested by decreased protein levels of peroxiredoxin, thioredoxin and thioredoxin reductase. Moreover, antioxidant N-acetylcysteine alleviated the cytotoxicity of G. pps. Pharmacological inhibition of SAPK/JNK and P38 alleviated the G. pps-mediated cytotoxicity. The extract activated apoptosis in leukemia and lymphoma patient cell samples but not in mononuclear cells from healthy donors further supporting the therapeutic values of G. pps for hematologic malignancies.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
Externí odkaz: