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Here, we report the cytotoxicity of extracts from mushroom <jats:italic>Gymnopilus purpureosquamulosus<\/jats:italic> H\u00f8il (<jats:italic>G<\/jats:italic>. <jats:italic>pps<\/jats:italic>) and describe its molecular mechanisms. Using leukemia, lymphoma and multiple myeloma cell lines, 28\u201335 ppm <jats:italic>G<\/jats:italic>. <jats:italic>pps<\/jats:italic> extract inhibited cell proliferation by ~46\u201379%, which correlates with activation of apoptosis as indicated by increase in annexin V-positive cells (~5\u20138-fold), production of reactive oxygen species (~2\u20133-fold), cells in sub G0\/G1 phase (~3\u201313-fold), caspase 3 enzymatic activity (~1.6\u20132.9-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 <jats:italic>G<\/jats:italic>. <jats:italic>pps<\/jats:italic>. Pharmacological inhibition of SAPK\/JNK and P38 alleviated the <jats:italic>G<\/jats:italic>. <jats:italic>pps<\/jats:italic>-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 <jats:italic>G<\/jats:italic>. <jats:italic>pps<\/jats:italic> for hematologic malignancies.<\/jats:p>","DOI":"10.1371\/journal.pone.0252541","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T19:47:24Z","timestamp":1622231244000},"page":"e0252541","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK\/JNK signaling pathway"],"prefix":"10.1371","volume":"16","author":[{"given":"Rich Milton","family":"Dulay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2471-8247","authenticated-orcid":true,"given":"Benigno C.","family":"Valdez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seemanti","family":"Chakrabarti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braham","family":"Dhillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofronio P.","family":"Kalaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato G.","family":"Reyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esperanza C.","family":"Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"pone.0252541.ref001","unstructured":"World Health Organization. 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