Molecular biology reports · 2026
Exploring the therapeutic potential of momordica balsamina: A focus on anticancer and nephroprotective effects.
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Kgakishe Mante, Maluleka Marole, Poopedi Kgomotso, Mampuru Leseilane, Mbazima Vusi
Аннотация
BACKGROUND: Despite being considered a gold standard chemotherapeutic drug, cisplatin is associated with dose-limiting toxicity, especially nephrotoxicity. 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 Momordica balsamina aqueous extract (MBAE) as an adjuvant to reduce cisplatin-induced kidney cell damage and death.
METHODS: 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.
RESULTS: 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 µg/ml at 24 h, while significantly reducing viability at 48 h. 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 µg/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 h 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.
CONCLUSION: The data indicate that the extract has significant potential as a renoprotective agent in cisplatin therapy.
METHODS: 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.
RESULTS: 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 µg/ml at 24 h, while significantly reducing viability at 48 h. 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 µg/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 h 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.
CONCLUSION: The data indicate that the extract has significant potential as a renoprotective agent in cisplatin therapy.