Polymethoxyflavones from citrus inhibited gastric cancer cell proliferation through inducing apoptosis by upregulating RARβ, both in vitro and in vivo

Wang, Yue; Chen, Yunyi; Zhang, He; Chen, Jiebiao; Cao, Ji; Chen, Qingjun; Li, Xian; Sun, Chongde

doi:10.1016/j.fct.2020.111811

Cited by 31 publications

(18 citation statements)

References 44 publications

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“…Studies have shown that tangeretin exhibited broad bioactivities including antioxidant, anti-inflammatory, antidiabetic, and neuroprotective effects [95][96][97][98]. It induces apoptosis in GC through the up-regulation of the RARB gene expression and activation of caspase-3, caspase-9, and PARP1 [99].…”

Section: Tangeretinmentioning

confidence: 99%

Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches

Kozak

Forma

Czeczelewski

et al. 2020

IJMS

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Epithelial-mesenchymal transition (EMT) constitutes one of the hallmarks of carcinogenesis consisting in the re-differentiation of the epithelial cells into mesenchymal ones changing the cellular phenotype into a malignant one. EMT has been shown to play a role in the malignant transformation and while occurring in the tumor microenvironment, it significantly affects the aggressiveness of gastric cancer, among others. Importantly, after EMT occurs, gastric cancer patients are more susceptible to the induction of resistance to various therapeutic agents, worsening the clinical outcome of patients. Therefore, there is an urgent need to search for the newest pharmacological agents targeting EMT to prevent further progression of gastric carcinogenesis and potential metastases. Therapies targeted at EMT might be combined with other currently available treatment modalities, which seems to be an effective strategy to treat gastric cancer patients. In this review, we have summarized recent advances in gastric cancer treatment in terms of targeting EMT specifically, such as the administration of polyphenols, resveratrol, tangeretin, luteolin, genistein, proton pump inhibitors, terpenes, other plant extracts, or inorganic compounds.

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Section: Tangeretinmentioning

confidence: 99%

Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches

Kozak

Forma

Czeczelewski

et al. 2020

IJMS

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“…The Quantitative Real‐Time Polymerase Chain Reaction (qRT‐PCR) was performed according to our previous report with small modifications (Wang et al., 2020). Briefly, cells were plated in 6‐well plates with densities of 2 × 10 6 cells per well for HL‐60.…”

Section: Methodsmentioning

confidence: 99%

Limonin induces apoptosis of HL‐60 cells by inhibiting NQO1 activity

Chen

Liang

et al. 2021

Food Science & Nutrition

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Limonin is an important bioactive substance in citrus fruits, especially in seeds, which has great potential in cancer prevention and treatment. In order to explore the anticancer activity based on interaction between limonin and NQO1, Human promyelocytic leukemia cells (HL‐60) were studied in vitro. We found that limonin could inhibit proliferation and promote apoptosis of HL‐60 cells, and the effect was positively correlated with its dosage. Western blot results showed that limonin could activate the endogenous apoptosis pathway mediated by mitochondria via up‐regulating pro‐apoptotic proteins (Bax, cytochrome c, Caspase3, and Caspase9) and down‐regulating anti‐apoptotic proteins (Bcl‐2), thus inhibiting the proliferation of HL‐60 cells and promoting apoptosis, which further proved the anticancer activity of limonin from the molecular mechanism. At the same time, limonin down‐regulated the expression of NQO1, indicating that limonin may indirectly act on the apoptosis pathway by regulating the expression activity of antioxidant enzymes in vivo, thus exerting its inhibitory effect on tumor cells, which provides an idea for the molecular mechanism that natural products can indirectly exert their anticancer effect by regulating the activity of antioxidant enzymes.

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“…Further, compound 53 demonstrated the capacity to induce autophagy in human keratinocyte HaCaT cells [67], vasodilatator effect in the rat aorta [68] and to protect the intestinal barrier from the demages induced by dextran sulfate sodium [69]. PMFs can be considered as especially promising lead compounds for cancer therapy as asignificant cytotoxic activity has been demonstrated toward a number of cancer cells [70,71] with several mechanisms of action [72,73]; the cytotypes investigated include MCF-7 [73][74][75][76], Hs578T triple-negative breast cancer [73,77]; colon cancer cells CaCo-2 [19], LoVo [78], HTC-116 [79,80] and HT-29 [79,81]; lung cancer cells A549 [80,82], H460 [82,83], H1299 [82,83]; gastric cancer cell lines AGS, BGC-823, and SGC-7901 [84]; leukemia cells HL-60 [85]. However, data regarding a possible antitumor activity in vivo are still rather uncommon.…”

Section: Flavanoidsmentioning

confidence: 99%

The Orange Peel: An Outstanding Source of Chemical Resources

Fontana¹

2021

Citrus - Research, Development and Biotechnology

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Citrus sinensis (L.) Osbeck is a very common cultivar belonging to the Rutaceae family. It is largely diffused in several areas of the world characterized by mild to warm climate conditions. Its abundant worldwide production (up to 107 Tons. per year) and consumption both as the edible part of the fruit and as several types of derivative products imply the production of a huge amount of waste, such as the fruit pomace. Several ways of recycling this material have been developed in recent years: employment as fertilizer, fodder ingredient, and even cloth material. However, the chemical added value of Citrus sinensis peel has been underestimated despite the diversified and significant content of useful chemicals, such as polyphenols, polymethoxylated phenols, glycosylated flavonoids, volatile and non-volatile terpenoids, pectins, enzymes, etc. This work aims to highlight the outstanding chemical potential of Citrus sinensis peel.

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Polymethoxyflavones from citrus inhibited gastric cancer cell proliferation through inducing apoptosis by upregulating RARβ, both in vitro and in vivo

Cited by 31 publications

References 44 publications

Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches

Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches

Limonin induces apoptosis of HL‐60 cells by inhibiting NQO1 activity

The Orange Peel: An Outstanding Source of Chemical Resources

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