Dietary phytochemicals in colorectal cancer prevention and treatment: A focus on the molecular mechanisms involved

Afrin, Sadia; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes‐Hernández, Tamara Y.; Cianciosi, Danila; Reboredo‐Rodríguez, Patricia; Zhang, Jiaojiao; Manna, Piera Pia; Daglia, Maria; Atanasov, Atanas G.; Battino, Maurizio

doi:10.1016/j.biotechadv.2018.11.011

Cited by 141 publications

(95 citation statements)

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“…It has been shown to modulate the function of many downstream substrates that are involved in regulating proliferation, invasion, apoptosis, and cell cycle. 34,35 In our present study, we demonstrated that DHM can remarkably inhibit the growth of CRC. In addition, we speculated whether DHM can activate NLRC3 expression and downregulate PI3K/mTOR pathway.…”

Section: Discussionsupporting

confidence: 63%

Dihydromethysticin, a natural molecule from Kava, suppresses the growth of colorectal cancer via the NLRC3/PI3K pathway

Pan

Liu

Wang

et al. 2020

Molecular Carcinogenesis

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Dihydromethysticin (DHM), a natural compound derived from Kava, has been reported to be effective against mental disorders and some malignant tu mors. However, little is known about the inhibitory effect of DHM on colorectal cancer (CRC). First, we examined the impact of DHM on human colon cancer cell lines, which demonstrated that DHM inhibits proliferation, migration, and invasion and promotes apoptosis and cell cycle arrest in colon cancer cells in vitro. Using small hairpin RNA, we inhibited nucleotide-oligomerization domain-like receptor subfamily C3 (NLRC3)/phosphoinositide 3-kinase (PI3K) pathway to elucidate the partial signaling of DHM-mediated tumor suppression. Additionally, using an ectopic human CRC model, we verified whether DHM inhibits tumor growth and angiogenesis via the NLRC3/PI3K pathway in vivo. Overall, DHM showed an inhibitory effect on CRC by altering cell proliferation, migration, invasion, apoptosis, cell cycle, and angiogenesis, possibly via the NLRC3/PI3K pathway. Thus, DHM may be a promising candidate for CRC therapy. K E Y W O R D S colorectal cancer, dihydromethysticin, NLRC3 1 | INTRODUCTION Colorectal cancer (CRC) is third most prevailing malignant tumor in the world. In 2016, approximately 134 490 individuals were diagnosed with CRC in the United States, and it was responsible for mortality of more than one-third. 1 In the past few decades, remarkable progress has been made in the treatment of CRC with variety of chemotherapy drugs and immunotherapies constantly emerging. However, due to drug resistance and dose-limiting toxicity, limited success has been achieved in treating advanced CRC. 2 Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CDK4, cyclin-dependent kinase 4; CK, creatine kinase.; CRC, colorectal cancer; DAPI, 4′, 6-diamidino-2-phenylindole; DHM, dihydromethysticin; H&E staining, hematoxylin and eosin staining; JNK, c-Jun NH2 terminal kinase; LDH, lactate dehydrogenase; MMP2, matrix metallopeptidase 2; MMP9, matrix metallopeptidase 9; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-kappa B; NLRC3, nucleotide-oligomerization domain-like receptor subfamily C3; PBS, phosphate-buffered saline; PI3K, phosphoinositide 3-kinase; RIPA, radio immunoprecipitation assay; TUNEL, terminal dUTP nick-end labeling; VEGF, vascular endothelial growth factor. Huayang Pan, Fukai Liu, and Jinge Wang contributed equally to this work. Terminal dUTP nick-end labeling (TUNEL) assay was performed according to the manufacturer's instructions (Roche, Shanghai, China). CRC cells were washed once with PBS, fixed with formalin for 30 minutes, and washed again with PBS. Cells were then suspended 576 | PAN ET AL.

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Section: Discussionsupporting

confidence: 63%

Dihydromethysticin, a natural molecule from Kava, suppresses the growth of colorectal cancer via the NLRC3/PI3K pathway

Pan

Liu

Wang

et al. 2020

Molecular Carcinogenesis

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“…One such strategy is to use another compound to sensitize NSCLC to gefitinib-induced apoptosis. Flavonoids are a wide class of polyphenols, which can exert effects in cancer chemoprevention because of their capability to interfere with signaling cascades responsible for carcinogenesis and metastasis that has been connected with multiple cell-regulatory activities in cancer cells [ 25 – 27 ]. Flavonoid compounds have been tested against cancer patients under varieties of clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Trifolium Flavonoids Overcome Gefitinib Resistance of Non-Small-Cell Lung Cancer Cell by Suppressing ERK and STAT3 Signaling Pathways

et al. 2020

BioMed Research International

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Gefitinib is a tyrosine kinase inhibitor of EGFR (epidermal growth factor receptor) and represents the first-line treatment for EGFR mutation patients with NSCLC (non-small-cell lung cancer) therapeutics. However, NSCLC patients are inclined to develop acquired gefitinib drug resistance through nowadays, unarticulated mechanisms of chemoresistance. Here, we investigated the role of TF (Trifolium flavonoids) on sensitizing gefitinib resistance in NSCLC cells and revealed its potential mechanism of action. We demonstrated that TF exerted significantly potential chemosensitivity in gefitinib resistant NSCLC cells. MTT assay and cytological methods were used to analyze cell viability and apoptosis in NSCLC cell line PC-9R. Both TF and gefitinib suppressed PC-9R cell growth in a dose-dependent manner. Subtoxic concentrations of TF did significantly augment gefitinib-induced apoptosis in PC-9R cell line. The TF promoted chemosensitivity was major mediated by the PARP and caspases activation. Meanwhile, the TF promoted chemosensitivity also decreased the expression of Bcl-2 and Mcl-1. Finally, TF significantly reduced the phosphorylation levels of STAT3 and ERK. Altogether, the results of the present study indicated the potential mechanisms of chemosensitivity of TF in gefitinib-induced apoptosis of NSCLC by downregulating ERK and STAT3 signaling pathways and Bcl2 and Mcl-1 expression and a promising application of TF in therapy of NSCLC with gefitinib resistant.

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“…Colorectal cancer (CRC) is one of the most highly diagnosed cancer, being the third most common in terms of occurrence in men and second in women, and the fourth cause of malignant cancer death worldwide (Afrin et al, 2020;Favoriti et al, 2016;Ferlay et al, 2014). Highest incidence in developed regions accounting to 55% and mortality rate of around 52% in less developed regions of the world were recorded (Ferlay et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Malignancy and high mortality rate were often attributed to hyperproliferation as well as metastasis, which involves the migration and spread of the primary tumor into nearby or surrounding tissue and organs. Hence, molecular mechanisms, which promote CRC progression, involving tumor growth, migration, angiogenesis, metastasis, and recurrence, have been targets in CRC treatment (Afrin et al, 2020;Jahangiri, Khalaj-kondori, Asadollahi, & Sadeghizadeh, 2019). Meanwhile, significant risk factors associated with CRC, which gained much attention, are the lifestyle and diet-related aspects, namely, lack of exercise, smoking, excessive amount of red and processed meat and fats in the diet, high alcohol consumption, obesity, and low intake of fiber-containing foods (Afrin et al, 2020;Gao, Guo, Gao, Zhu, & Qin, 2015;Terzić, Grivennikov, Karin, & Karin, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Since CRC has been vastly linked with dietary factors, the effects of natural products and phytochemicals in the prevention and alleviation of the disease have been a focus of many studies. These dietary phytochemicals exert their chemopreventive effects against CRC through targeting series of cell signaling pathways, such as NF-κB, Wnt/β-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK (Afrin et al, 2016(Afrin et al, , 2018Raffa, Maggio, Raimondi, Plescia, & Daidone, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Extracts of Elaeagnus multiflora Thunb. fruit fermented by lactic acid bacteria inhibit SW480 human colon adenocarcinoma via induction of cell cycle arrest and suppression of metastatic potential

Lizardo

Cho

Lee

et al. 2020

Journal of Food Science

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Elaeagnus multiflora Thunb. (cherry silverberry, CS) is an underutilized fruit with notable phytochemical profile and biological activities. However, there are few studies on cancer inhibitory effect using fermented CS fruits. This study aimed to develop fermented CS fruits using lactic acid bacteria and investigate its anticolorectal cancer (CRC) property and phenolic composition. SW480 CRC cells were treated with aqueous extracts of CS fermented by single and coculture of Lactobacillus plantarum and L. casei. The extracts of fermented CS exhibited greater antiproliferative activity and anticlonogenicity in comparison with the unfermented extract and the control. Among the extracts of CS fruits, the ones fermented by the coculture (LPLC) showed the most potent tumor suppression property, at 25 to 50 µg/mL, by induction of cell cycle arrest at the S and G2/M phases, downregulating cyclins and its dependent kinases while increasing tumor suppressor proteins p27 and p53. LPLC also exerted its tumor suppression effect by inhibiting the chemotactic motility and invasiveness of SW480 cells, downregulating matrix metalloproteinase‐9, and PI3K/AKT/mTOR pathways and upregulating TIMP‐9, and E‐cadherin. HPLC‐PDA analysis revealed that the levels of major flavonoids in CS extracts, namely, catechin, epigallocatechin, epicatechin, epigallocatechin gallate, rutin, naringin, and quercetin, were enhanced by fermentation with L. plantarum and L. casei in coculture. Overall, this study showed that the extracts of fermented CS have augmented and multifaceted anticancer property and can be utilized in the development of functional food or ingredient for the prevention of CRC. Practical Application Elaeagnus multiflora, commonly known as cherry silverberry, has been proven to contain bioactive components and possesses high functionality. However, due to limited shelf‐life as a fresh commodity, development of novel product is essential. Fermentation is a beneficial process employed in the food industry to enhance the shelf stability, nutritional, sensory, and functional properties of food products. The present study has explored the possibility of adding value to an underutilized fruit, cherry silverberry, through the process of fermentation, making it as a potential source of functional food and ingredient for the prevention of colorectal cancer.

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Dietary phytochemicals in colorectal cancer prevention and treatment: A focus on the molecular mechanisms involved

Cited by 141 publications

References 304 publications

Dihydromethysticin, a natural molecule from Kava, suppresses the growth of colorectal cancer via the NLRC3/PI3K pathway

Dihydromethysticin, a natural molecule from Kava, suppresses the growth of colorectal cancer via the NLRC3/PI3K pathway

Trifolium Flavonoids Overcome Gefitinib Resistance of Non-Small-Cell Lung Cancer Cell by Suppressing ERK and STAT3 Signaling Pathways

Extracts of Elaeagnus multiflora Thunb. fruit fermented by lactic acid bacteria inhibit SW480 human colon adenocarcinoma via induction of cell cycle arrest and suppression of metastatic potential

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