Harmaline downregulates angiogenesis markers and suppresses the growth of 4T1 breast cancer cells in vivo and in vitro

Rashidi, Mohsen; Mahmoudian, Elham; Mirzaei, Sepideh; Mazloomi, Seyadeh Narges; Bazi, Ali; Azadeh, Hossein; Mozaffari, Mobina

doi:10.1016/j.cbi.2022.110087

Cited by 10 publications

(8 citation statements)

References 38 publications

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“…day 37), the animals were euthanized. The doses for hesperidin and doxorubicin in individual and combination therapy were selected according to previous studies 20–22 …”

Section: Methodsmentioning

confidence: 99%

Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer

Shakiba

Bazi

Ghasemi

et al. 2023

J Cellular Molecular Medi

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Considering the unfavourable response of breast cancer (BC) to treatment, we assessed the therapeutic potential hesperidin in mice bearing 4T1 BC tumours. Anti‐tumour effects were assessed by measuring pathologic complete response (pCR), survival analysis, immunohistochemistry for E‐cadherin, VEGF, MMP9, MMP2 and Ki‐67, serum measurement of IFNγ and IL‐4, and gene expression analysis of CD105, VEGFa, VEGFR2 and COX2. Survival of tumour‐bearing mice was the highest in mice receiving a combination of hesperidin and doxorubicin (Dox) (80%) compared to the normal saline (43%), hesperidin 5 (54%), 10 (55.5%), 10 (60.5%) and 40 (66%) mg/kg, and 10 mg/kg Dox‐treated (73%) groups (p < 0.0001 for all). Compared to the normal saline group, there was a significant elevation in IFNγ level in the animals receiving 20 (p = 0.0026) and 40 (p < 0.001) mg/kg hesperidin, 10 mg/kg Dox (p < 0.001), and combined hesperidin (20 mg/kg) and Dox (10 mg/kg) (p < 0.001). A significant reduction in the gene expression of CD 105 (p = 0.0106), VEGFa (p < 0.0001), VEGFR2 (p < 0.0001), and Cox2 (p = 0.034) and a significant higher pCR score (p = 0.006) were noticed in mice treated with 10 mg/kg Dox + 20 mg/kg hesperidin compared to those treated with 10 mg/kg Dox alone. Immunohistochemical staining showed significant reductions in Ki‐67 (p < 0.001) and VEGF (p < 0.001) and a significant elevation in E‐cadherin (p = 0.005) in the 10 mg/kg Dox + 20 mg/kg treatment group than in 10 mg/kg Dox alone group. Hesperidin can be considered as a potentially suitable anti‐cancer agent for BC that can synergize with other chemotherapeutics.

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“…day 37), the animals were euthanized. The doses for hesperidin and doxorubicin in individual and combination therapy were selected according to previous studies 20–22 …”

Section: Methodsmentioning

confidence: 99%

Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer

Shakiba

Bazi

Ghasemi

et al. 2023

J Cellular Molecular Medi

Self Cite

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“…[100] In mouse models of breast tumor, the effects of various harmaline dosages, either alone or in conjunction with doxorubicin (DOX), were evaluated. [101] In this study, 4T1 cells were subcutaneously injected into Balb/c mice to produce breast tumors. Normal saline, harmaline alone (10, 20, or 30 μg kg À 1 ), or harmaline (20 μg kg À 1 ) + DOX (10 μg kg À 1 ) were given to the mice.…”

Section: Dna Damage and Epigenetic Modificationsmentioning

confidence: 99%

“…Harman reduced the ability of Chinese hamster cells to repair DNA damage and correct mutations, probably due to the intercalation properties of this substance [100] . In mouse models of breast tumor, the effects of various harmaline dosages, either alone or in conjunction with doxorubicin (DOX), were evaluated [101] . In this study, 4T1 cells were subcutaneously injected into Balb/c mice to produce breast tumors.…”

Section: β‐Carbolines’ Anticancer Activity Through Modulation Of Hall...mentioning

confidence: 99%

Anticancer Potential of β‐Carboline Alkaloids: An Updated Mechanistic Overview

Tshikhudo,

Mabhaudhi,

Koorbanally

et al. 2024

Chemistry & Biodiversity

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This comprehensive review is designed to evaluate the anticancer properties of β‐carbolines derived from medicinal plants, with the ultimate goal of assessing their suitability and potential in cancer treatment, management, and prevention. An exhaustive literature survey was conducted on a wide array of β‐carbolines including, but not limited to, harmaline, harmine, harmicine, harman, harmol, harmalol, pinoline, tetrahydroharmine, tryptoline, cordysinin C, cordysinin D, norharmane, and perlolyrine. Various analytical techniques were employed to identify and screen these compounds, followed by a detailed analysis of their anticancer mechanisms. Natural β‐carbolines such as harmaline and harmine have shown promising inhibitory effects on the growth of cancer cells, as evidenced by multiple in vitro and in vivo studies. Synthetically derived β‐carbolines also displayed noteworthy anticancer, neuroprotective, and cognitive‐enhancing effects. The current body of research emphasizes the potential of β‐carbolines as a unique source of bioactive compounds for cancer treatment. The diverse range of β‐carbolines derived from medicinal plants can offer valuable insights into the development of new therapeutic strategies for cancer management and prevention.

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“…In particular, the current study focused on the potential anticancer effects of harmaline, which were originally investigated in the 1970s (Nasehi et al., 2016 ). The ability of harmaline to modulate the cellular and signal transductions implicated in oxidative balance, DNA integrity maintenance, cell cycle progression, and apoptosis regulation appears to be the basis for the antitumor effects of this alkaloid (Bhattacharjee et al., 2018 ; Rashidi et al., 2022 ). It has been reported that harmaline can suppress the proliferative activity of several cancerous cells, including esophageal squamous cell carcinoma (ESCC) (Zhang et al., 2021 ), myeloma (Boeira et al., 2001 ), as well as lung (Roy et al., 2020 ), breast (Rashidi et al., 2022 ), liver (Xu et al., 2018 ), and gastric cancers (Wang et al., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

“…The ability of harmaline to modulate the cellular and signal transductions implicated in oxidative balance, DNA integrity maintenance, cell cycle progression, and apoptosis regulation appears to be the basis for the antitumor effects of this alkaloid (Bhattacharjee et al., 2018 ; Rashidi et al., 2022 ). It has been reported that harmaline can suppress the proliferative activity of several cancerous cells, including esophageal squamous cell carcinoma (ESCC) (Zhang et al., 2021 ), myeloma (Boeira et al., 2001 ), as well as lung (Roy et al., 2020 ), breast (Rashidi et al., 2022 ), liver (Xu et al., 2018 ), and gastric cancers (Wang et al., 2015 ). Furthermore, in terms of harmaline's anticancer effects, this alkaloid can be used as an herbal adjuvant alongside chemotherapeutic drugs to assess the drug's efficacy on cancerous cells (Rashidi et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Harmaline induces apoptosis and inhibits migration in A2780 ovarian cancer cells in vitro

Shariat Razavi,

Taghdisi Khaboushan,

Jafari

et al. 2024

Physiological Reports

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Ovarian cancer is one of the most prevalent malignancies in women. Harmaline is reported to have powerful anticancer properties. We aimed to investigate the apoptotic and antimetastatic properties of harmaline in A2780 ovarian cancer cells. Cell viability, apoptosis, migration, and invasion were investigated in cells treated with harmaline. Reactive oxygen species (ROS) production, mRNA expression of apoptosis‐associated genes, MMP‐2, and MMP‐9 were measured. Harmaline attenuated the viability of A2780 ovarian cancer cells in a dose‐ and time‐dependent way. Furthermore, compared to NIH/3T3 mouse normal cell line (IC50 = 417 μM), the malignant A2080 cells were more sensitive to harmaline (IC50 = 300 μM after 24 h). Harmaline increased the production of ROS, raised the mRNA expression of p53 and the Bax/Bcl2 ratio. Harmaline also increased the proportion of cells in the late apoptotic and necrotic phases. MMP‐2 and MMP‐9's mRNA expression, gelatinase activity, and migration of A2780 cells also decreased by harmaline. These findings suggest that harmaline may have the potential to be a therapeutic drug for ovarian cancer by triggering apoptosis and suppressing invasion and migration.

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Harmaline downregulates angiogenesis markers and suppresses the growth of 4T1 breast cancer cells in vivo and in vitro

Cited by 10 publications

References 38 publications

Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer

Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer

Anticancer Potential of β‐Carboline Alkaloids: An Updated Mechanistic Overview

Harmaline induces apoptosis and inhibits migration in A2780 ovarian cancer cells in vitro

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