The Potential of Matrine in the Treatment of Breast Cancer: A Review
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. In Vitro Experimental Study of MT on Breast Cancer Cells
3.2. Analysis of In Vivo Experimental Studies of MT Against Breast Cancer Cell Lines
4. Molecular Mechanisms of MT in Breast Cancer
4.1. Cytotoxic Effects of MT in Breast Cancer Cells
4.2. Induction of Cancer Cell Cycle Arrest by MT
4.3. Induction of Apoptosis in Cancer Cells by MT
4.4. Induction of Autophagy in Cancer Cells by MT
4.5. Inhibition of Angiogenesis by MT
4.6. Inhibition of Cancer Cell Metastasis
4.7. Regulation of Immune Function by MT
4.8. Reversing Drug Resistance in Cancer Cells by MT
5. Medications and Combination Therapies of MT
6. Pharmacokinetics and Toxicological Profile of MT
6.1. Pharmacokinetics and Dose Optimization
6.2. Toxicological Profile and Reported Adverse Effects
7. Summary and Prospect
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
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Familia | Genus | Name | Part Used | Reference |
---|---|---|---|---|
Leguminosae | Sophora L. | Sophora flavescens Aiton | Roots | Yang et al., 2024 [15] |
Leguminosae | Sophora L. | Sophora alopecuroides L. | Fruits | Chen et al., 2023 [16] |
Leguminosae | Sophora L. | Sophora xanthoantha C. Y. Ma | Flowers, buds | Chi ZL, 2011 [17] |
Leguminosae | Sophora L. | Sophora davidii Kom. ex Pavol. | Stem, leaf, flower, seed, roots | Xu et al., 2023 [18] |
Leguminosae | Sophora L. | Sophora mollis Graham. | Roots | Peng et al., 2010 [19] |
Leguminosae | Sophora L. | Sophora pachycarpa Schrenk ex C. A. Mey | Roots | Zheng et al., 1996 [20] |
Leguminosae | Sophora L. | Sophora dunnii Prain | Roots | Ling et al., 2000 [21] |
Leguminosae | Sophora L. | Sophora moorcroftiana (Benth.) Baker | Seeds | Zhao et al., 2020 [22] |
Leguminosae | Sophora L. | Sophora tonkinensis Gagnep. | Seeds | Zou et al., 2023 [23] |
Leguminosae | Styphnolobium Schott | Styphnolobium japonicum (L.) Schott | Flowers, leaves, branches, roots, fruits | Wang et al., 2018 [24] |
Leguminosae | Euchresta J. Benn. | Euchresta japonica Benth. ex Oliv. | Roots | Yuan et al., 2023 [25] |
Leguminosae | Euchresta J. Benn. | Euchresta formosana (Hayata) Ohwi | Roots | Li et al., 2014 [26] |
Leguminosae | Euchresta J. Benn. | Euchresta horsfieldii (Lesch.) J. Benn.) | Roots | Li et al., 2014 [26] |
Leguminosae | Euchresta J. Benn. | Euchresta tubulosa Dunn | Roots | Li et al., 2014 [26] |
Solanaceae Juss. | Lycium L. | Lycium chinense Miller | Fruits | Zhang et al., 2024 [27] |
Bignoniaceae Juss. | Incarvillea Juss. | Incarvillea sinensis Lam. | Grass | Song et al., 2023 [28] |
Cells Type | Composition (mg·mL −1) | Time of Administration (h) | Cell Proliferation Inhibition Rate/ Cell Apoptosis | Influenced Gene/ Protein | Other | Ref. |
---|---|---|---|---|---|---|
MCF-7 | MT | 48 | Cell proliferation was detected by MTT assay, and the IC50 value was 0.68 ± 2.00 mg·mL−1. | NA | NA | Liu et al., 2008 [50] |
MCF-7 | MT | 24, 48, 72 | Cell proliferation was detected by MTT assay, and the IC50 value was 0.93 ± 9.03 mg·mL−1. | NA | NA | Mao et al., 2019 [51] |
MCF-7 | MT | 48 | The cell survival rate detected by the MTT method with 4.0 mg·mL−1 MT was 43.13 ± 5.37%. | Significant decrease in p-JAK2, p-STAT3 protein levels. | NA | Wang et al., 2023 [52] |
MCF-7 | MT | 48 | The cell survival rate detected by MTT assay, and the IC50 value was 0.85 mg·mL−1. | LC3-I/LC3-II levels were significantly increased, and Beclin-1 protein expression was increased. | NA | Jia et al., 2023 [53] |
MCF-7 | MT | NA | Cell proliferation was detected by MTT assay, and the IC50 value was 15.8 mg·mL−1. | NA | NA | Sun et al., 2017 [54] |
MCF-7 | MT | 72 | Cell proliferation was detected by MTT assay, and the IC50 value was 4.83 mg·mL−1. Cycle retention in the G1 phase, S phase, and G2/M phase cell numbers decreased. | The expression of p21 and p27 was upregulated, p53 and cyclin-D1 were downregulated, and the accumulation of LC3-II was increased. | NA | Ou, 2014 [55] |
MCF-7 | MT | 48 | Cell proliferation was detected by MTT assay, and the IC50 value was 2.00 ± 0.17 mg·mL−1, and it showed concentration-dependent inhibition. | Bax protein expression was upregulated. | NA | Zhao et al., 2018 [56] |
MCF-7 | MT | 24, 48, 72 | The inhibition rate at 72 h of action time with 4.0 mg·mL−1 MT was 73.29 ± 4.07%, and it showed concentration-dependent inhibition. Cell proliferation was stagnant in the G0/G1 phase, and the number of cells in S phase was reduced. | Bax protein expression was upregulated and downregulated Bcl-2 protein expression. | NA | Sui, 2013 [57] |
MCF-7 | MT | 24, 48, 72 | The inhibition rate at 72 h of action time with 2.0 mg·mL−1 MT was 68. 31 ± 2.13% and it showed concentration-dependent inhibition and promoted apoptosis. | Decreased mitochondrial transmembrane potential and increased Bax expression. | NA | Wang et al., 2012 [58] |
MCF-7 | MT | 24 | The inhibition rate at 24 h of action time with 2.0 mg·mL−1 MT was 19.63 ± 0.17%. | Decreased mitochondrial transmembrane potential. | Cells show shortened protrusions, reduced cytoplasm, intracytoplasmic vacuoles, and nuclear consolidation and fragmentation. | Li et al., 2011 [59] |
MCF-7 | MT | 24, 48, 72 | The inhibition rate at 72 h of action time with 2.0 mg·mL−1 MT was 67.16 ± 2.14%, and it showed concentration-dependent inhibition. The apoptosis rate of 2.0 mg·mL−1 MT for 24 h was 20.16 ± 0.16%. | Decreased mitochondrial transmembrane potential | NA | Gu et al., 2015 [60] |
MCF-7 | MT | 24 | Significantly inhibited growth and promoted apoptosis. | Upregulation of Fas protein expression and downregulation of VEGF protein and telomerase activity gradually decreased with increasing concentrations of MT. | Cells show shortened protrusions, reduced cytoplasm, and nuclear consolidation and fragmentation with a budding of the cell membrane. | Li et al., 2013 [61] |
MCF-7 | MT | 24 | The MTT assay showed a concentration- and time-dependent inhibition rate of 22.35 ± 0.84% for mg·mL−1 MT at 24 h. | Decreased p-pg, MRP1 protein, and p-AKT protein expression in the PI3K/AKT-signaling pathway and increased PTEN protein expression. | NA | Wei et al., 2016 [62] |
MCF-7 | MT | 72 | The inhibition rate of MCF-7/ADR cells at 1.25 mg·mL−1 MT was 66.2% with an IC50 of 0.92 mg·mL−1. The proportion of S-phase cells increased, and the proportion of G2/M cells decreased. | NA | Cytosol shrinkage and cytoplasmic condensation. | Zhou et al., 2003 [63] |
MCF-7 | MT | 24 | After 24 h, the concentrations of 2.0 mg·mL−1 and 2.4 mg·mL−1 of MT induced the late apoptosis rate to be 23.5% ± 0.024 and 56.82% ± 0.042. The IC50 at 24 h was 2.729 mg·mL−1. | Inhibits the expression of IL-6, JAK1, P-JAK1, STAT3, and P-STAT3 proteins by a molecular mechanism that may be related to its effective regulation of the IL-6/STAT3 pathway. | NA | Ren, 2023 [64] |
MDA-MB-231 | MT | 24, 48, 72 | The inhibition rate at 72 h of action time with 5 mg·mL−1 MT was 67.41%. | Downregulation of HN1 protein expression and decreased expression of VEGF and CD31. | NA | Guo, 2022 [65] |
Bcap-37 | MT | 48 | The inhibition rate at 48 h of action time with 2.0 mg·mL−1 MT was 18.25 ± 1.12%. | Decreased Cyclin D1 and c-Myc protein expression. | NA | Xiao et al., 2018 [66] |
4T1 | MT | 48 | The inhibition rate at 48 h of action time with 0.4 mg·mL−1 MT was 17.32 ± 3.09%. | Significantly decreased ANXA3 protein expression. | NA | Shi et al., 2018 [67] |
SK-BR-3 | MT | 48 | The inhibition rate at 48 h of action time with 3.0 mg·mL−1 MT was 46.6 ± 3.2% and showed concentration-dependent inhibition. | Inhibition of miR-21 expression and upregulation of PTEN protein expression. | NA | Xiao et al., 2018 [68] |
MCF-7 | MT | 72 | Cell proliferation was detected by MTT assay, and the IC50 value was 0.92 mg·mL−1. | The relative expression of Bcl-2 and p65 was decreased, and the relative expression of Bax, PARP, and GSK-3β genes was increased. | NA | Zhou et al., 2017 [69] |
Bcap-37 | MT | 24, 48, 72 | Cell proliferation was detected by MTT assay, proliferation inhibition existed in a concentration and time-dependent manner, and the apoptosis rate was 19.58% at 24 h of the action time of 2 mg·mL−1. | LC3b-II expression was upregulated. | NA | Ren et al., 2014 [70] |
MDA-MB-231 | MT | 48 | MTT assay was used to detect cell proliferation, and the inhibition rate was 49.21 ± 1.12% at 0.2 mg·mL−1 action time 48 h. | It may be related to PI3K/Akt and MAPK/ERK-signaling pathway. | NA | Yu et al., 2016 [71] |
MCF-7/ADR cell | MT | 24 | The MTT assay showed a concentration- and time-dependent inhibition rate of 11.82 ± 0.66% for 0.6 mg·mL−1 at 24 h. | Decreased expression of MDR1, MRP1, and AKT gene and increased expression of PTEN gene. | NA | Wei et al., 2014 [72] |
Bcap-37 | MT | 24, 48, 72 | Cell proliferation was detected by MTT assay, and the proliferation inhibition was concentration- and time-dependent with IC50s of 0.63, 0.42, and 0.29 mg·mL−1 at 24, 48, and 72 h. | The expression of caspase-3 and Bax proteins was increased, and the expression of Bcl-2 protein was decreased. | NA | Zheng et al., 2012 [73] |
Bcap-37 | MT | 24, 48, 72 | The highest apoptosis rate of 6.90 ± 0.19% was observed when the action time of 0.08 mg·mL−1 was 48 h. | The expression of p53 and Bax proteins was increased, and Bcl-2 protein was decreased. | NA | Zheng et al., 2012 [74] |
MCF-7 | MT | 24, 48, 72 | Cell proliferation was detected by MTT assay, and proliferation inhibition was concentration- and time-dependent, with inhibition rates ranging from 10.86% to 70.23% at 72 h. | Bax protein expression was increased, and Bc-l2 protein was decreased. | NA | Li et al., 2011 [75] |
Bcap-37 | MT | 24, 48, 72 | Cell proliferation was detected by MTT assay, and proliferation inhibition was concentration- and time-dependent. | Increased expression of p53 and Bax proteins and decreased expression of Bcl-2 proteins. | Decreased cytoplasm, rounding, and vacuolization of cells. | Zheng et al., 2012 [76] |
MCF-7/ADR cell | MT | 48 | Cell proliferation was detected by MTT assay, and proliferation inhibition was concentration- and time-dependent. | Increased expression of Fas and bax proteins and decreased Bcl-2 proteins. | NA | Zhou et al., 2007 [77] |
MCF-7 | MT | 24 | Cellular autophagy phenomenon was obvious and concentration-dependent. | The expression of Beclin-1 was increased, and PI3K, Akt, and TOR were decreased. | NA | Jia et al., 2023 [78] |
MCF-7 | MT | 24 | MTT results showed that the IC50 of MT for MCF-7 was 1.38 ± 0.09 mg·mL−1. | The expression of P-gp was decreased. | NA | Li et al., 2013 [79] |
Bcap | MT | 72 | The MTT assay showed that the inhibition rate of 0.1 mg·mL−1 was less than 40% for 72 h. | NA | NA | Wang et al., 1996 [80] |
MCF-7 | MT | 24, 48, 72 | CCK-8 test showed MT inhibited cancer cell proliferation in a time-dose-dependent manner, and the apoptosis rate was 72.81±3.83% at 8 mg·mL−1 of MT. | Reduced p62 expression and p-AKT/AKT ratio. | Cells showed contraction, membrane blistering, balloon-like protrusions, and partial detachment. | Du et al., 2020 [81] |
MCF-7 BT-474 MDA-MB-231 | MT | 48 | 3 mg·mL−1 MT resulted in a reduction of cell number to 15.5–23.6% by MTT assay, and MDA-MB-231 was the most sensitive cell. 3 mg·mL−1 MT acted for 48 h, and the apoptosis rate was about 90%. | Reduced IKKβ expression, which may be related to the NF-κB-signaling pathway. | NA | Shao et al., 2018 [82] |
MCF-7 | MT | 24, 48, 72 | MTT assay showed that it inhibited cell proliferation in a concentration- and time-dependent manner and induced apoptosis with an IC50 value of 0.86 mg·mL−1 at 48 h. | Inhibited the expression of vascular endothelial growth factor and down-regulated the Wnt/β-catenin pathway. | NA | Xiao et al., 2018 [83] |
MCF-7 | MT | 24, 48, 72 | MTT assay showed that MT inhibited cell growth in a concentration- and time-dependent manner with an IC50 (48 h) of approximately 0.8 mg·mL−1. After the action of MT with 0.8 mg·mL−1, the apoptosis rate was 25.6 ± 4.8%, inducing cell cycle arrest in G1/S phase. | Increased expression of PTEN, p21/WAF1/CIP1, p27/KIP1 and decreased expression of pAkt, pBad | NA | Li et al., 2019 [84] |
MCF-7 T47-D | MT | 24, 48, 72 | MTT assay showed that MT inhibited cell growth in a concentration- and time-dependent manner with an IC50 (48 h) of approximately 0.8 mg·mL−1. | Increased expression of Let-7b and decreased expression of CD133, KLF4. | NA | Liang et al., 2019 [85] |
MDA-MB-231 MCF-7 | MT | 24, 48 | MTT assay showed that MT inhibited cell growth in a concentration- and time-dependent manner and induced apoptosis. | Increased expression of E-calmodulin and decreased expression of N-calmodulin and waveform protein. | MT(2 mg/mL) significantly inhibited cell migration. | Ren et al., 2020 [86] |
MCF-7 | MT | 48 | MTT assay showed MT significantly inhibited cell proliferation and induced cell apoptosis. S-phase cells decreased and G0/G1-phase cells increased. | Bax protein expression increased and Bcl-2 protein expression decreased. | NA | Shi et al., 2015 [87] |
MDA-MB-453 HCC-1806 | MT | NA | CCK-8 tests indicate that MT inhibits cell proliferation and promotes apoptosis. | HN1 protein expression is inhibited and Cleared-Caspase-3 protein expression is increased. | NA | Guo et al., 2023 [88] |
MCF-7 | MT | 24, 48, 72 | Cell viability was detected by MTT assay with an IC50 value of 0.53 ± 34.6 mg·mL−1.MT promoted apoptosis. | Promoted the release of cytochrome C and enhances caspase-3 activity, while p-eIF2a was elevated. | NA | Xiao et al., 2017 [89] |
MCF-7 | MT | 24, 48, 72 | MTT assay showed that the inhibition of cell proliferation after 72 h was 10.86–70.23% in a time- and concentration-dependent manner, and the apoptosis rate was 4.17–19.63% in the 0.25–2.0 mg·mL−1 MT group. | Increased expression of Bax and decreased expression of Bcl-2. | NA | Li et al., 2015 [90] |
BT-20 MCF-7 | MT | 48 | The IC50 values of cell viability after 48 h were 0.31 ± 23.45 mg·mL−1 and 0.22 ± 16.89 mg·mL−1 as detected by the MTT assay. | NA | NA | Jiang et al., 2017 [91] |
MCF-7 | MT | 24, 48, 72 | Cell survival was 77.5%, and apoptosis was 32.6% as detected by flow cytometry. | NA | NA | Zhang et al., 2016 [92] |
MDA-MB-231 MDA-MB-468 | MT | 24, 48, 72 | MT inhibited cell proliferation, and flow cytometry results showed that MT blocked the cell cycle and induced apoptosis. | Inhibition of BCL-2 expression and up-regulation of caspase-3, LC3-II expression. | NA | Wei et al., 2023 [93] |
MCF-7 | MT | 24, 48, 72 | MTT assay showed that MT inhibited cell growth in a concentration- and time-dependent manner and induced apoptosis. | Decreased Bcl-2/Bax ratio, downregulated VEGF and VEGFR-2 expression, and increased caspase-3 and caspase-9. | NA | Li et al., 2010 [94] |
MCF-7 MDA-MB-231 | MT | 8, 16, 24 | MTT assay showed that MT inhibited cell growth in a concentration- and time-dependent manner. | Increased expression of Akt, Erk1/2, and p38. | NA | Zou et al., 2019 [95] |
MDA-MB-231 | MT | NA | The inhibition rate of cell proliferation after 0.1 mg·mL−1 of MT was 20.29 ± 0.84% as determined by MTT assay. | NA | NA | Thang PNT et al., 2022 [96] |
MCF-7 | MT | 48 | The MTT assay showed MT inhibited cell viability in a concentration-dependent manner, and the IC50 value for cell viability after 48 h was 0.53 mg·mL−1. | NA | NA | Mousavi SH et al., 2014 [97] |
MDA-MB-231 | MT | 24, 48, 72 | MTT assay showed that MT inhibited cell growth in a concentration- and time-dependent manner. | Decreased Bcl-2/Bax protein and decreased mRNA levels of MMP-9, MMP-2, EGF, and VEGFR1. | NA | Yu et al., 2009 [98] |
MDA-MB-231 | MT | 24 | MT inhibited cell growth and induced apoptosis. | Increased caspase-3 activation. | NA | Chui CH et al., 2005 [99] |
Cells Type | Composition/Concentration | Dosage | Time Administer Drug | Methods | Results | Ref. |
---|---|---|---|---|---|---|
4T1 | MT, 3.5–7.5 mg·mL−1 | 10 mL·kg−1 | 10 | Mice in the modeling group were inoculated with 0.2 mL of 1 × 106 cells-mL−1 of single-cell suspension of mouse 4T1 breast cancer cells in the right axilla, and after successful modeling, mice were injected with MT once/d for 10 d. | The tumor weight of mice in groups of MT was reduced, and the number of apoptotic cells was higher. The effect may be related to the activation of the JNK1/AP-1-signaling pathway and the regulation of p53, Bax, and other apoptosis-related proteins. | Dong, 2019 [100] |
MDA-MB-231 | MT, 20 mg·mL−1 | 50 mL·kg−1 | 15 | The nude mice were inoculated with 1 × 107 cells-mL−1 of MDA-MB-231 cell suspension under the right mammary gland, and MT 50 mg/kg was injected intraperitoneally five times/week for a total of 15 times. | Tumor growth was inhibited in nude mice after the administration of MT. MT can induce apoptosis. At day 22, the inhibition of tumor volume by ascorbic acid alone was 28.72%. | Guo et al., 2022 [65] |
Walker 256 | MT, 0.5–20 mg·mL−1 | 10 mL·kg−1 | 28 | Rats were subcutaneously inoculated with 0.4 mL of Walker 256 breast cancer cell suspension (5 × 107 cells-mL−1) in the right axilla. The drug was administered intraperitoneally at a volume of 10 mL·kg−1 twice/day for 14 d. | The tumor inhibition rates of the low-, medium-, and high-dose groups of MT were 24.6%, 31.7%, and 36.3%, respectively, showing a dose-dependent inhibition of tumor growth. | Zhang et al., 2018 [101] |
MA737 | MT, NA | 20 mL·kg−1 | 28 | MA737 cells 1 × 105 cells/mouse were inoculated subcutaneously in the right inguinal area, randomly grouped, and sacrificed 14 days after administration, and thymus, spleen, and tumor weights, as well as body weights of the mice, were weighed. | MT can increase the weight of the thymus and spleen, and the weight of the tumor is smaller. After the treatment of MT, the TH/TS ratio of mice is significantly increased, which can improve the immunity of mice. | Mao et al., 1996 [102] |
MDA-MB-453 | MT, NA | NA | NA | NA | MT inhibited tumor growth and decreased the expression of HN1 protein but promoted the protein expression of Cleared-Caspase-3. | Guo Q et al., 2023 [88] |
4T1 | MT, NA | NA | 14 | Injected 4 × 104 4T1 cells into the left inguinal mammary fat pads of mice, after 15 days, received daily i.p. injection of MT for 14 days, and then euthanized, and the tumors, lungs, and livers were removed. | The volume of tumors of mice treated with MT was significantly smaller, and the numbers of tumor on the lung and livers surface of MT-treated mice were lowered. | Li H et al., 2010 [94] |
4T1 | MT, NA | NA | 21 | Injected 4 × 104 4T1 cells (100 µL, 5 × 106 cells-mL−1) into the right side of the fourth mammary gland of mice, mice received i.p. injection of MT, the mice were sacrificed on day 21, and the tumors were removed rapidly and weighed. | MT can inhibit the growth of tumors and induce apoptosis while decreasing the level of VEGF. | Xiao X et al., 2018 [83] |
TM40D | MT, 5–20 mg·mL−1 | 10 mL·kg−1 | 20 | TM40D cells with cell density adjusted to 2.0 × 107 cells-mL−1, subcutaneous injection of 0.1 mL per nude mouse’s back, and intraperitoneal injection of the corresponding dose of drug. On the 20th day, the mice were euthanized, and tumor blocks were removed and weighed. | MT can reduce tumor weight and promote cancer cell apoptosis. | Bai et al., 2016 [103] |
MCF-7/ADR | MT, 50, 100 mg·mL−1 | NA | 21 | Nude mice were subcutaneously inoculated with MCF-7/ADR cells. MT was injected for 21 days, and the tumor inhibition rate was measured using in vivo tumor inhibition experiments. | The tumor inhibition rates of the high-dose and low-dose groups of MT were 60.7% and 42.1%. MT can promote cancer cell apoptosis. | Zhou et al., 2017 [104] |
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Yang, Y.; Li, Y.; Liao, S.; Gao, P.; Tian, J.; Fu, C.; Qin, X.; Jin, S. The Potential of Matrine in the Treatment of Breast Cancer: A Review. Biomedicines 2025, 13, 1355. https://doi.org/10.3390/biomedicines13061355
Yang Y, Li Y, Liao S, Gao P, Tian J, Fu C, Qin X, Jin S. The Potential of Matrine in the Treatment of Breast Cancer: A Review. Biomedicines. 2025; 13(6):1355. https://doi.org/10.3390/biomedicines13061355
Chicago/Turabian StyleYang, Yumin, Yufeng Li, Shanshan Liao, Pan Gao, Jie Tian, Cheng Fu, Xuhua Qin, and Shenrui Jin. 2025. "The Potential of Matrine in the Treatment of Breast Cancer: A Review" Biomedicines 13, no. 6: 1355. https://doi.org/10.3390/biomedicines13061355
APA StyleYang, Y., Li, Y., Liao, S., Gao, P., Tian, J., Fu, C., Qin, X., & Jin, S. (2025). The Potential of Matrine in the Treatment of Breast Cancer: A Review. Biomedicines, 13(6), 1355. https://doi.org/10.3390/biomedicines13061355