Nobiletin, a citrus polymethoxyflavone, enhances the effects of bicalutamide on prostate cancer cells<i>via</i>down regulation of NF-κB, STAT3, and ERK activation

Ma, Yuran; Ren, Xiang; Patel, Nandini; Xu, Xuetao; Wu, Panpan; Liu, Wenfeng; Zhang, Kun; Goodin, Susan; Li, Dongli; Zheng, Xi

doi:10.1039/c9ra10020b

Cited by 19 publications

(5 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In hepatocellular carcinoma cells, hesperetin induces the activation of apoptosis-inducing factors by mediating the excessive production of intracellular ROS and increasing Ca 2+ levels [ 34 ]. Nobiletin, a polymethoxyflavone present in citrus fruits, has a synergistic effect in inhibiting colony formation and inducing apoptosis of prostate cancer cells when combined with anti-androgen drugs used for prostate cancer therapy [ 35 ]. Hesperidin is also a major compound found in citrus fruits and is well known for its wide range of pharmacological effects, such as anti-inflammatory, anti-allergic, and anti-viral effects [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Hesperidin Suppresses the Proliferation of Prostate Cancer Cells by Inducing Oxidative Stress and Disrupting Ca2+ Homeostasis

et al. 2022

View full text Add to dashboard Cite

Although androgen deprivation therapy is mainly used for its treatment, the mortality rate of prostate cancer remains high due to drug resistance. Hence, there is a need to discover new compounds that exhibit therapeutic effects against prostate cancer with minimum side effects. Hesperidin is a flavonoid carbohydrate isolated from citrus fruits. It has antiproliferative effects in various cancer types; however, whether it can modulate cell proliferation by modulating the key targets of cancer therapy, including intracellular signaling pathways and oxidative stress, remains unknown. Therefore, we confirmed that hesperidin suppressed the proliferation of prostate cancer cells, PC3 and DU145. Hesperidin induced cell death by regulating the cell cycle and inhibited the expression of proliferating cell nuclear antigen, a cell proliferation marker. Hesperidin also promoted the generation of reactive oxygen species and induced mitochondrial membrane depolarization and endoplasmic reticulum stress in prostate cancer cells. Moreover, as hesperidin increased Ca2+ levels in prostate cancer cells, we co-treated the inositol 1,4,5-trisphosphate receptor inhibitor, 2-aminoethyl diphenyl borate (2-APB), with hesperidin. Notably, 2-APB restored cell proliferation, which was reduced to control levels by hesperidin. In addition, hesperidin inhibited the activation of the phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways. Hesperidin also enhanced the anticancer effects of the chemotherapeutic agent, cisplatin, in both PC3 and DU145 cells. Taken together, these results suggest that hesperidin can be used as a potential therapeutic adjuvant in prostate cancer as it can inhibit cell proliferation by mediating oxidative stress and increasing Ca2+ levels.

show abstract

Section: Discussionmentioning

confidence: 99%

Hesperidin Suppresses the Proliferation of Prostate Cancer Cells by Inducing Oxidative Stress and Disrupting Ca2+ Homeostasis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…PMFs, especially nobiletin, have been combined with other anti-cancer agents to fight against cancer in vitro and in vivo. Cell-based assays suggested that nobiletin enhanced the anti-cancer abilities of imatinib and bicalutamide against chronic myeloid leukaemia cells [60] and prostate cancer cells [72] ,…”

Section: Synergistic Anti-cancer Effects With Other Agentsmentioning

confidence: 99%

Natural sources, refined extraction, biosynthesis, metabolism, and bioactivities of dietary polymethoxyflavones (PMFs)

Gan¹,

Liu²,

Li³

et al. 2024

Food Science and Human Wellness

View full text Add to dashboard Cite

Polymethoxyflavones (PMFs) are a type of uncommon dietary flavonoids, characterized by more than one methoxy group, which exist in limited plant species, like Citrus species and Kaempferia parviflora. In addition, different PMFs, such as nobiletin, sinensetin, tangeretin, and casticin, have been isolated from these natural sources. PMFs have received increasing attention due to their multiple bioactivities, such as antioxidant, anti-inflammatory, anti-cancer, metabolic regulatory, immunoregulatory, neuroprotective, and skin protective effects. These bioactivities of PMFs should be associated with the regulation of critical molecular targets and the interaction with gut microbiota. In order to provide a comprehensive and updated review of PMFs, their natural sources, refined extraction, biosynthesis, metabolism, and bioactivities are summarised and discussed, with the emphasis on the molecular mechanisms of PMFs on regulating different chronic diseases. Overall, PMFs may be promising flavonoids to the forefront of nutraceuticals for the prevention and/or treatment of certain human chronic diseases.

show abstract

“…Polymethoxylated flavones have been highlighted for their anti-inflammation [30] and anticancer effects [31] in recent years. However, the effects of nobiletin and tangeretin on eNOS expression in human endothelial cells have not been investigated.…”

Section: Differential Effects Of Citrus Flavonoids On Enos Expressionmentioning

confidence: 99%

Nobiletin Protects Endothelial Cell Function via Upregulation of eNOS/ET-1 and Antioxidant Status-Related Genes under Nonstimulated and Inflammatory Conditions

Zhang

Pieri

et al. 2022

Journal of Food Quality

View full text Add to dashboard Cite

Nobiletin, a natural polymethoxylated flavonoid compound, has been shown to exert a wide range of biological activities. However, there is limited evidence on the molecular mechanisms by which nobiletin modulates endothelial cell function. Our aim was to investigate the potential of nobiletin to enhance endothelial cell functionality under nonstimulated and inflammatory conditions. To this end, gene expression relevant to nitric oxide (NO) production, endothelin 1 (ET-1), and antioxidant status in human endothelial cells EA.hy926 was determined using real-time PCR. The fluorescence probe 4,5-diaminofluorescein (DAF-2) was used to measure NO production. The results demonstrated significant upregulation of eNOS and antioxidant genes as well as downregulation of ET-1 by nobiletin under nonstimulated and TNF-α-stimulated inflammatory conditions. These findings suggest a promising protective effect of nobiletin with relevance for cardiovascular health, likely through the NO/ET-1 dynamics and Nrf2 signaling pathway.

show abstract

Nobiletin, a citrus polymethoxyflavone, enhances the effects of bicalutamide on prostate cancer cellsviadown regulation of NF-κB, STAT3, and ERK activation

Abstract: Nobiletin enhance the anticancer effect of bicalutamide on prostate cancer cells via down regulation of NF-κB, STAT3, Erk activation.

Cited by 19 publications

References 46 publications

Hesperidin Suppresses the Proliferation of Prostate Cancer Cells by Inducing Oxidative Stress and Disrupting Ca2+ Homeostasis

Hesperidin Suppresses the Proliferation of Prostate Cancer Cells by Inducing Oxidative Stress and Disrupting Ca2+ Homeostasis

Natural sources, refined extraction, biosynthesis, metabolism, and bioactivities of dietary polymethoxyflavones (PMFs)

Nobiletin Protects Endothelial Cell Function via Upregulation of eNOS/ET-1 and Antioxidant Status-Related Genes under Nonstimulated and Inflammatory Conditions

Contact Info

Product

Resources

About