Hesperetin modulates TGFβ induced metastatic potential of prostate cancer cells by altering histone methylation marks

Dalpatraj, Nidhi; Tak, Jyoti; Naik, Ankit; Thakur, Noopur

doi:10.1016/j.adcanc.2022.100077

Cited by 2 publications

(2 citation statements)

References 26 publications

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“…Isorhamnetin had a significant inhibitory effect on the invasion and migration of A549 cells ( Luo et al, 2019 ). In addition, hesperetin, licochalcone B, ellagic acid have been demonstrated to possess the ability to inhibit the metastasis of cancer cells ( Zhao et al, 2014 ; Kim et al, 2021 ; Dalpatraj et al, 2022 ). Thus, the effect of C. oleifera bud EE on inhibiting the metastasis of A549 cells may be related to these active constituents.…”

Section: Discussionmentioning

confidence: 99%

Phytochemical analysis and anticancer effect of Camellia oleifera bud ethanol extract in non-small cell lung cancer A549 cells

Niu,

Jia,

Yang

et al. 2024

Front. Pharmacol.

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Camellia oleifera is a medicine food homology plant widely cultivated in the Yangtze River Basin and southern China due to its camellia oil. Camellia oleifera bud and fruit exist simultaneously, and its bud is largely discarded as waste. However, C. oleifera bud has been used in traditional Chinese medicine to treat a variety of ailments. Thus, the purpose of this study was to identify the chemical components of C. oleifera bud ethanol extract (EE) and first evaluate its anticancer effects in non-small cell lung cancer A549 cells. Based on UHPLC-Q-Orbitrap-MS analysis, seventy components were identified. For anticancer activity, C. oleifera bud EE had remarkable cytotoxic effect on non-small cell lung cancer A549 (IC50: 57.53 ± 1.54 μg/mL) and NCI-H1299 (IC50: 131.67 ± 4.32 μg/mL) cells, while showed lower cytotoxicity on non-cancerous MRC-5 (IC50 > 320 μg/mL) and L929 (IC50: 179.84 ± 1.08 μg/mL) cells. It dramatically inhibited the proliferation of A549 cells by inducing cell cycle arrest at the G1 phase. Additionally, it induced apoptosis in A549 cells through a mitochondria-mediated pathway, which decreased mitochondrial membrane potential, upregulated Bax, activated caspase 9 and caspase 3, and resulted in PARP cleavage. Wound healing and transwell invasion assays demonstrated that C. oleifera bud EE inhibited the migration and invasion of A549 cells in a dose-dependent manner. The above findings indicated that C. oleifera bud EE revealed notable anticancer effects by inhibiting proliferation, inducing apoptosis, and suppressing migration and invasion of A549 cells. Hence, C. oleifera bud ethanol extract could serve as a new source of natural anticancer drugs.

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Section: Discussionmentioning

confidence: 99%

Phytochemical analysis and anticancer effect of Camellia oleifera bud ethanol extract in non-small cell lung cancer A549 cells

Niu,

Jia,

Yang

et al. 2024

Front. Pharmacol.

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“…Since phytochemicals have multiple targets and lower systemic toxicity, they are more advantageous for cancer prevention and treatment, as compared to drugs with single molecular targets [23]. In our previous study, we showed that hesperetin, a citrus bioflavonoid, could induce cell cycle arrest and inhibit TGFβ-induced EMT, invasion, and migration of prostate cancer cells [24].…”

Section: Of 17mentioning

confidence: 99%

Combination Treatment of a Phytochemical and a Histone Demethylase Inhibitor—A Novel Approach towards Targeting TGFβ-Induced EMT, Invasion, and Migration in Prostate Cancer

Dalpatraj

Naik

Thakur

2023

IJMS

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Minimizing side effects, overcoming cancer drug resistance, and preventing metastasis of cancer cells are of growing interest in current cancer therapeutics. Phytochemicals are being researched in depth as they are protective to normal cells and have fewer side effects. Hesperetin is a citrus bioflavonoid known to inhibit TGFβ-induced epithelial-to-mesenchymal transition (EMT), migration, and invasion of prostate cancer cells. Targeting epigenetic modifications that cause cancer is another class of upcoming therapeutics, as these changes are reversible. Global H3K27me3 levels have been found to be reduced in invasive prostate adenocarcinomas. Combining a demethylase inhibitor and a known anti-cancer phytochemical is a unique approach to targeting cancer to attain the aforementioned objectives. In the current study, we used an H3K27 demethylase (JMJD3/KDM6B) inhibitor to study its effects on TGFβ-induced EMT in prostate cancer cells. We then gave a combined hesperetin and GSK-J4 treatment to the PC-3 and LNCaP cells. There was a dose-dependent increase in cytotoxicity and inhibition of TGFβ-induced migration and invasion of prostate cancer cells after GSK-J4 treatment. GSK-J4 not only induced trimethylation of H3K27 but also induced the trimethylation of H3K4. Surprisingly, there was a reduction in the H3K9me3 levels. GSK-J4 alone and a combination of hesperetin and GSK-J4 treatment effectively inhibit the important hallmarks of cancer, such as cell proliferation, migration, and invasion, by altering the epigenetic landscape of cancer cells.

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Hesperetin modulates TGFβ induced metastatic potential of prostate cancer cells by altering histone methylation marks

Cited by 2 publications

References 26 publications

Phytochemical analysis and anticancer effect of Camellia oleifera bud ethanol extract in non-small cell lung cancer A549 cells

Phytochemical analysis and anticancer effect of Camellia oleifera bud ethanol extract in non-small cell lung cancer A549 cells

Combination Treatment of a Phytochemical and a Histone Demethylase Inhibitor—A Novel Approach towards Targeting TGFβ-Induced EMT, Invasion, and Migration in Prostate Cancer

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