{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:53:16Z","timestamp":1785412396589,"version":"3.56.0"},"reference-count":31,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Bialystok","award":["B.SUB.25.359"],"award-info":[{"award-number":["B.SUB.25.359"]}]},{"award":["B.SUB.25.359"],"award-info":[{"award-number":["B.SUB.25.359"]}],"id":[{"id":"https:\/\/ror.org\/00y4ya841","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Prostate cancer progression and therapy response are strongly influenced by the tumor microenvironment (TME), particularly stromal fibroblasts that regulate survival signaling, metabolism, and drug resistance. In this study, we investigated whether extracts from three Lepidium meyenii (maca) morphotypes, yellow (MY), red (MR), and black (MB), modulate doxorubicin (DOX) responses in 22Rv1 prostate cancer cells under mono-culture and co-culture conditions with human dermal fibroblasts (HDFa). Cell viability, proliferation, apoptosis-related proteins, lipid droplets (LDs) accumulation, and selected signaling markers were analyzed. In mono-culture, maca extracts exhibited limited cytotoxicity, with MB showing the strongest but still moderate effect. Co-treatment with DOX did not enhance cytotoxicity and resulted in context-dependent modulation of caspase-3 and caspase-8. In co-culture, HDFa cells reduced DOX sensitivity, suggesting altered treatment responses under co-culture conditions. Morphometric analysis suggested fibroblast activation-like changes. Across models, maca reduced LDs accumulation, while increased adipose triglyceride lipase (ATGL) levels in co-culture suggested altered lipid utilization. Additionally, maca extracts modulated PI3K, PSMA, FOXO1, FAP, and HAT1 in a morphotype-dependent manner. Overall, maca extracts acted primarily as context-dependent modulators of signaling and lipid metabolism markers rather than direct cytotoxic agents with their effects strongly dependent on both extract type and microenvironmental context.<\/jats:p>","DOI":"10.3390\/cells15121090","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T09:06:52Z","timestamp":1781600812000},"page":"1090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Context-Dependent Effects of Maca Extracts on Signaling, Apoptosis, and Lipid Metabolism Markers in Prostate Cancer Mono- and Co-Culture Models"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7989-0207","authenticated-orcid":false,"given":"Adam Jan","family":"Olichwier","sequence":"first","affiliation":[{"name":"Radiopharmacy Centre, Medical University of Bialystok, 15-569 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7614-8957","authenticated-orcid":false,"given":"Magdalena","family":"Bruzgo-Grzybko","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy and Radiopharmacy, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela Suwda","family":"Kalita","sequence":"additional","affiliation":[{"name":"Radiopharmacy Centre, Medical University of Bialystok, 15-569 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Golonko","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1454-647X","authenticated-orcid":false,"given":"Natalia","family":"Bielicka","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy and Radiopharmacy, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Chabielska","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy and Radiopharmacy, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gromotowicz-Poplawska","sequence":"additional","affiliation":[{"name":"Radiopharmacy Centre, Medical University of Bialystok, 15-569 Bialystok, Poland"},{"name":"Department of Biopharmacy and Radiopharmacy, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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