The Role of Mitochondrial Dysfunction in Cytotoxic Effects of Solanum nigrum Water Extract on MCF-7 and MDA-MB-231 Breast Cancer Cells

Khan, Haseeb A.; Alghamdi, Amani A.; Prasad, N. Rajendra; Alrokayan, Salman H.; Almansour, Basma S.; Hatamilah, Ashraf A. K.

doi:10.31083/j.fbl2808180

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…The intracellular ATP levels were determined after the exposure of PBTDG and erlotinib (0-100 μM) to MCF-7 cells for 12 h using a colorimetric ATP assay kit (Sigma-Aldrich, USA) as reported earlier [ 42 ]. The unknown concentrations of the test samples were calculated using the linear standard curve generated from the concentration of 0-12 nmole ATP.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells

Khan,

Isab,

Alhomida

et al. 2024

ACAMC

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Background: Platinum complexes are commonly used for cancer chemotherapy; however, they are not only highly-priced but also have various side effects. It is, therefore, important to design affordable anticancer drugs with minimal side effects. background: Platinum complexes are commonly used for cancer chemotherapy however they are not only highly priced but also have various side effects. It is therefore important to design affordable anticancer drugs with minimal side effects. Methods: We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS) digold(I)} (abbreviated as PBTDG) and tested its cytotoxicity of MCF-7 breast cancer cells. We also evaluated the effects of PBTDG on mitochondrial membrane potential, generation of reactive oxygen species (ROS) and apoptosis in breast cancer cells. objective: To synthesize a novel gold(I) complex and test its cytotoxicity and apoptotic potential in MCF-7 breast cancer cells. Results: The IC50 values for PBTDG and sorafenib were found to be 1.48 μM and 4.45 μM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-fold apoptosis for 1 μM, 3 μM, and 10 μM concentrations, respectively. The induction of apoptosis by the same concentrations of sorafenib was 1.2, 1.3, and 1.6-fold, respectively. The low concentration of PBTDG (1 μM) induced the generation of ROS by 99.83%, which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentrations (5 μM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively. method: We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS)digold(I)} (abbreviated as PBTDG) and tested the cytotoxicity in MCF-7 breast cancer cells using MTT assay. We used spectrophotometry for ATP analysis and flow cytometry for mitochondrial potential, apoptosis and ROS analyses. Conclusion: The lower concentration of PBTDG produced similar cytotoxicity and apoptotic effects that were caused by a comparatively higher concentration of known anticancer drug (sorafenib). The anticancer effects of PBTDG are attributed to its tendency to disrupt mitochondrial membrane potential, induction of apoptosis and generation of ROS. Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer. result: The IC50 values for PBTDG and sorafenib were found to be 1.48 μM and 4.45 μM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-folds apoptosis for 1 µM, 3 µM, and 10 µM concentrations, respectively. The induction of apoptosis by same concentrations of sorafenib was 1.2, 1.3, and 1.6-folds, respectively. The low concentration of PBTDG (1 µM) induced the generation of reactive oxygen species (ROS) by 99.83% which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentration (5 µM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively. other: Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer.

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Section: Methodsmentioning

confidence: 99%

Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells

Khan,

Isab,

Alhomida

et al. 2024

ACAMC

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EFHD1 expression is correlated with tumor-infiltrating neutrophils and predicts prognosis in gastric cancer

Zhao,

Wang,

Xue

et al. 2023

Heliyon

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Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer

Adu-Amankwaah,

Februarie,

Nyambo

et al. 2024

Preprint

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Triple-negative breast cancer (TNBC) represents a significant global health crisis due to its resistance to conventional therapies and lack of specific molecular targets. This study explored the potential of Eriocephalus racemosus (E. racemosus) as an alternative treatment for TNBC. The cytotoxic properties and high-resolution respirometry mitochondrial activities of E. racemosus against the MDA-MB 231 TNBC cell line were evaluated. Methods: Hexane solvent and bioactive fraction extractions of E. racemosus were performed, while mass spectrometry-based metabolite profiling was used to identify the phytochemical constituents of the extracts. The extracts were further tested against MDA-MB 231 cancer cells to determine their cytotoxicity. The mode of cell death was confirmed using flow cytometry. The activities of caspases 3, 8, and 9 were assessed using a multiplex activity assay kit. Glycolytic activity and High-resolution respirometry measurements of mitochondrial function in the MDA-MB 231 cell line were conducted using the Oroboros O2K. Results: Metabolite profiling of E. racemosus extracts identified the presence of coumarins, flavonoids, sesquiterpenoids, triterpenoids, and unknown compounds. The extracts demonstrated promising cytotoxic activities, with a half maximal inhibitory concentration (IC50) of 12.84 µg/mL for the crude hexane extract and 15.49 µg/mL for the bioactive fraction. Further, the crude hexane and bioactive fraction extracts induced apoptosis in the MDA-MB-231 cancer cell line, similar to the reference drug cisplatin (17.44%, 17.26% and 20.25%, respectively) when compared with untreated cells. Caspase 3 activities confirmed the induction of the apoptosis pathway in both cisplatin and the plant extracts. Additionally, caspase 8 and 9 activities confirmed the activation of both the intrinsic and extrinsic apoptosis pathways in the plant extracts. Increased levels of glycolytic activities were observed in the crude hexane extract. High-resolution respiratory measurements showed elevated mitochondrial activities in all components examined except for complex-IV activities. Conclusion: These findings support further exploration of E. racemosus as a potential therapeutic agent for TNBC, offering a promising avenue for the development of targeted treatments with minimal adverse effects.

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The Role of Mitochondrial Dysfunction in Cytotoxic Effects of Solanum nigrum Water Extract on MCF-7 and MDA-MB-231 Breast Cancer Cells

Cited by 3 publications

References 48 publications

Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells

Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells

EFHD1 expression is correlated with tumor-infiltrating neutrophils and predicts prognosis in gastric cancer

Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer

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