Brassinin Inhibits Proliferation in Human Liver Cancer Cells via Mitochondrial Dysfunction

Hong, Taeyeon; Ham, Jiyeon; Song, Jisoo; Song, Gwonhwa; Lim, Whasun

doi:10.3390/cells10020332

Cited by 22 publications

(28 citation statements)

References 42 publications

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“…It has been a very well proven fact that mitochondria play a very pivotal role in intrinsic apoptotic pathway (Davidson et al., 2020; Peña‐Blanco & García‐Sáez, 2018). Intracellular ROS generation can damage biological macromolecules, lipid membrane, leading to protein denaturation (Hong et al., 2021; Kiskova et al., 2020). These events initiate the intrinsic apoptotic pathway (D'Onofrio et al., 2020).…”

Section: Discussionmentioning

confidence: 99%

Targeting Jab1 using hesperidin (dietary phytocompound) for inducing apoptosis in HeLa cervical cancer cells

2021

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Plant flavonoids have been emerged as a potent anticancerous agent by exhibiting significant growth inhibitory potential and apoptotic induction in several carcinomas via targeting several oncoproteins. However, inverse association of hesperidin with Jab1 oncoprotein in cervical cancer has rarely been reported. Thus, we have intended our research study towards establishing this unexplored inverse correlation of hesperidin with Jab1 which could further prevent cervical cancer progression. Our research findings clearly demonstrated that hesperidin treatment resulted in Jab1 gene down‐regulation and p27 up‐regulation in a dose‐dependent manner in HeLa cancer cells. These gene modulations might occur via excessive reactive oxygen species (ROS) generation and caspase‐3 activation which further resulted in apoptotic induction. Increase in apoptotic cells was confirmed through Hoechst staining and cell cycle analysis. Thus, these results strongly suggested that Jab1 is a potent therapeutic target of hesperidin to suppress cell growth and trigger apoptosis in HeLa cells. Practical applications Dietary flavonoids play a crucial role in the management of numerous malignancies via targeting several mutated oncogenes. Our study strongly exhibited that hesperidin treatment suppressed the HeLa cancer cell proliferation via increased ROS generation and reduced Jab1 mRNA expression. Thus, the inference of Jab1‐mediated intracellular signals by hesperidin might be a novel approach to control cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Targeting Jab1 using hesperidin (dietary phytocompound) for inducing apoptosis in HeLa cervical cancer cells

2021

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“…Previous studies reported an anti-cancer activity of brassinin on several types of cancer, including colon [ 3 ], liver [ 4 ], prostate [ 24 ], and lung cancer [ 5 , 25 ]. However, the effects of brassinin on TNBC development have not been reported so far.…”

Section: Discussionmentioning

confidence: 99%

“…Such a compound is brassinin, a phytoalexin isolated from cruciferous vegetables, including cabbage, broccoli, and mustard greens [ 1 ]. Previous in-vitro studies demonstrated anti-proliferative and cytotoxic effects of brassinin on human colorectal [ 2 , 3 ], liver [ 4 ], and lung cancer cells [ 5 ]. In addition, brassinin has been shown to enhance the anti-cancer effects of paclitaxel in a A549 lung cancer xenograft mouse model [ 5 ] and an autochthonous mouse model of mammary gland tumors [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Brassinin Promotes the Degradation of Tie2 and FGFR1 in Endothelial Cells and Inhibits Triple-Negative Breast Cancer Angiogenesis

Becker

Qiu

et al. 2022

Cancers

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Brassinin, a phytoalexin derived from cruciferous vegetables, has been reported to exhibit anti-cancer activity in multiple cancer types. However, its effects on triple-negative breast cancer (TNBC) development and the underlying mechanisms have not been elucidated so far. In this study, we demonstrated in vitro that brassinin preferentially reduces the viability of endothelial cells (ECs) when compared to other cell types of the tumor microenvironment, including TNBC cells, pericytes, and fibroblasts. Moreover, brassinin at non-cytotoxic doses significantly suppressed the proliferation, migration, tube formation, and spheroid sprouting of ECs. It also efficiently inhibited angiogenesis in an ex-vivo aortic ring assay and an in-vivo Matrigel plug assay. Daily intraperitoneal injection of brassinin significantly reduced tumor size, microvessel density, as well as the perfusion of tumor microvessels in a dorsal skinfold chamber model of TNBC. Mechanistic analyses showed that brassinin selectively stimulates the degradation of Tie2 and fibroblast growth factor receptor 1 in ECs, leading to the down-regulation of the AKT and extracellular signal-regulated kinase pathways. These findings demonstrate a preferential and potent anti-angiogenic activity of brassinin, which may be the main mechanism of its anti-tumor action. Accordingly, this phytochemical represents a promising candidate for the future anti-angiogenic treatment of TNBC.

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“…Alpinumisoflavone (50 µM) or DMSO-treated cell suspensions were seeded to the lids of culture dishes and maintained for 72 h for imaging purposes. The ImageJ software was used for analysis of the spheroid surface [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…Lastly, after several washing steps, the nuclei were labeled with 5 µg/mL 4′, 6-diamidino-2-phenylindole (DAPI). The images were acquired using a confocal microscope (LSM710, Carl Zeiss, Oberkochen, Germany) [ 20 , 21 ].…”

Section: Methodsmentioning

confidence: 99%

Alpinumisoflavone Impairs Mitochondrial Respiration via Oxidative Stress and MAPK/PI3K Regulation in Hepatocellular Carcinoma Cells

et al. 2022

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Alpinumisoflavone is a natural prenylated isoflavonoid extracted from the raw fruit of Cudrania tricuspidata. Several studies have reported the beneficial characteristics of alpinumisoflavone, such as its antioxidant, anti-inflammation, anti-bacterial, osteoprotective, and neuroprotective effects. Alpinumisoflavone also has anti-cancer effects on thyroid, renal, and ovarian cancers, but its therapeutic effects on hepatocellular carcinoma (HCC) have not yet been demonstrated. We investigated the anti-cancer effects of alpinumisoflavone on HCC using human liver cancer cell lines, Hep3B and Huh7. Our results confirmed that alpinumisoflavone inhibited viability and regulated the MAPK/PI3K pathway in Hep3B and Huh7 cells. We also verified that alpinumisoflavone can depolarize the mitochondrial membrane potential and suppress the mitochondrial respiration in HCC cells. Moreover, we confirmed the dysregulation of the mitochondrial complexes I, III, and V involving mitochondrial oxidative phosphorylation at the mRNA level and the accumulation of calcium ions in the mitochondrial matrix. Lastly, we demonstrated that alpinumisoflavone induced mitochondria-mediated apoptosis via regulation of the Bcl-xL and BAK proteins. This study elucidates the anti-cancer effects of alpinumisoflavone on HCC.

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Brassinin Inhibits Proliferation in Human Liver Cancer Cells via Mitochondrial Dysfunction

Cited by 22 publications

References 42 publications

Targeting Jab1 using hesperidin (dietary phytocompound) for inducing apoptosis in HeLa cervical cancer cells

Targeting Jab1 using hesperidin (dietary phytocompound) for inducing apoptosis in HeLa cervical cancer cells

Brassinin Promotes the Degradation of Tie2 and FGFR1 in Endothelial Cells and Inhibits Triple-Negative Breast Cancer Angiogenesis

Alpinumisoflavone Impairs Mitochondrial Respiration via Oxidative Stress and MAPK/PI3K Regulation in Hepatocellular Carcinoma Cells

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