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This highlights the need for safe and effective adjuvant agents that protect against cisplatin-induced toxicity without affecting its anticancer activity. This study investigated the potential of\n                      <jats:italic>Momordica balsamina<\/jats:italic>\n                      aqueous extract (MBAE) as an adjuvant to reduce cisplatin-induced kidney cell damage and death.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The phytochemical analysis of the extract was done using Gas Chromatography-Mass Spectrometry. The effects of the extract in combination with cisplatin on cell viability in 2D and 3D cultures of HEK-293 and MDA-MB-231 cells were assessed using CCK-8, CellTiter-Glo 3D, and spheroid growth assays, respectively. Cell death in 2D HEK-293 and MDA-MB-231 cultures was assessed using Annexin V-FITC. DNA damage and cell cycle progression were analyzed using multicolor DNA damage and cell cycle analysis assays, respectively, while protein expression was determined by Western blotting in 2D HEK-293 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A sum of 26 compounds, ranging from terpenoids, furans, steroids, flavanols and azaflavanols were tentatively identified. The combinatorial treatments increased HEK-293 viability in 2D and 3D cultures as well as enhanced spheroid diameter and growth. Comparatively, the co-treatment increased MDA-MB-231 cell viability in 2D models following treatment with 800\u00a0\u00b5g\/ml at 24\u00a0h, while significantly reducing viability at 48\u00a0h. No notable changes in MDA-MB-231 spheroid diameters were observed although growth rate and spheroid viability decreased. The combinatory treatments increased early apoptotic cell death in a time-dependent manner in HEK-293 cells. On the other hand, a concentration- and time-dependent increase in late apoptotic cells percentages was observed in MDA-MB-231 cells. Cell cycle analysis revealed MBAE modulated the cell cycle by halting cells in the G0\/G1-phase following treatment with 200\u00a0\u00b5g\/ml while 800 ug\/ml supplementation promoted cell cycling by shifting cell cycle arrest from the S-phase to the G2\/M phase. Furthermore, a concentration-dependent decrease in pATM, pH2A.X, and co-activation was observed, although DNA damage worsened after 48\u00a0h of exposure. The combinatorial treatments modulated Bax\/Bcl-2 ratios while upregulating p53, p21, and PARP1 protein expression to prioritize DNA repair over cell death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The data indicate that the extract has significant potential as a renoprotective agent in cisplatin therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11033-026-12383-9","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:44:12Z","timestamp":1784537052000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the therapeutic potential of momordica balsamina: A focus on anticancer and nephroprotective effects"],"prefix":"10.1007","volume":"53","author":[{"given":"Mante","family":"Kgakishe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marole","family":"Maluleka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kgomotso","family":"Poopedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leseilane","family":"Mampuru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5212-1347","authenticated-orcid":false,"given":"Vusi","family":"Mbazima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"issue":"3","key":"12383_CR1","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.3390\/ijms23031532","volume":"23","author":"S Dasari","year":"2022","unstructured":"Dasari S, Njiki S, Mbemi A, Yedjou CG, Tchounwou PB (2022) Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy. 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