Anti‐tumor effects of crocetin and related molecular targets

Moradzadeh, Maliheh; Sadeghnia, Hamid Reza; Tabarraei, Alijan; Sahebkar, Amirhossein

doi:10.1002/jcp.25953

Cited by 42 publications

(24 citation statements)

References 85 publications

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“…A number of previous researches have elucidated that crocetin can inhibit cancer with different mechanisms, such as anti-proliferative and anti-metastatic actions, as well as inducing apoptosis, inhibiting nucleic acid synthesis and enhancing anti-oxidative system [45]. In the present study, the data revealed that crocetin suppressed GC progression via inhibiting angiogenesis, cell proliferation and EMTmediated metastasis of GC cells and these inhibitory effects of crocetin were associated with attenuated activation of Shh/Gli signaling pathway.…”

Section: Discussionsupporting

confidence: 52%

Crocetin suppresses angiogenesis through inhibiting Sonic hedgehog signaling pathway in gastric cancer

Zhou

Zang

Hou

et al. 2020

Preprint

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BackgroundCrocetin is an active component of saffron stigma, which has important therapeutic effects on various diseases including tumors, arthritis, hemorrhages, etc. However, the effects of crocetin on gastric cancer (GC) cells and their underlying mechanisms remain unclear.MethodsCell counting kit‑8 (CCK‑8), transwell assays, F-actin staining, tube formation and vasculogenic mimicry (VM) assays were used to examine the effects of crocetin on cell proliferation, migration and angiogenesis in GC. Enzyme linked immunosorbent assay (ELISA) and Western blot assay were performed to evaluate expression level of Sonic hedgehog (Shh) signaling and activation of epithelial‑mesenchymal transition (EMT) in GC cells treated with or without crocetin. Proliferation of xenograft tumors was detected by immunohistochemistry. ResultsCrocetin significantly inhibited tube formation of human umbilical vein endothelial (HUVEC) cells and VM formation of GC cells, as well as its proliferation, invasion and migration. Crocetin destroyed cytoskeleton and mosaic vessels formed by HUVEC and GC cells. Furthermore, we found that crocetin suppressed cell proliferation, migration, EMT, tube and VM formation through inhibiting Shh signaling pathway. Utilization of recombinant Shh reversed the suppressing effects of crocetin on cell proliferation, migration, angiogenesis and EMT. In addition, anti-tumor effect of crocetin was confirmed in xenograft tumors.ConclusionsCrocetin suppressed GC progression by inhibiting cell proliferation, migration and angiogenesis including tubes formed by HUVEC cells and VM vessels formed by GC cells, which were mediated by suppressing Shh signaling pathway. These results indicated that crocetin may function as an effective therapeutic drug against GC.

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Section: Discussionsupporting

confidence: 52%

Crocetin suppresses angiogenesis through inhibiting Sonic hedgehog signaling pathway in gastric cancer

Zhou

Zang

Hou

et al. 2020

Preprint

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“…However, resistance to this drug and its toxicity are major problems in the treatment of APL (Tomita et al, ). Plant‐derived bioactive compounds have been shown in numerous studies to exert a variety of antitumor actions, making them potential candidates for adjuvant therapy of different types of cancer (Karthick & Tandon, ; Mirzaei et al, ; Momtazi et al, ; Moradzadeh, Sadeghnia, Tabarraei, & Sahebkar, ). In the previous study, we showed that EGCG increased apoptosis and inhibited telomerase activity in breast cancer cells (Moradzadeh, Sadeghnia, Tabarraei, & Sahebkar, ).…”

Section: Discussionmentioning

confidence: 99%

“…Plant‐derived bioactive compounds have been shown in numerous studies to exert a variety of antitumor actions, making them potential candidates for adjuvant therapy of different types of cancer (Karthick & Tandon, ; Mirzaei et al, ; Momtazi et al, ; Moradzadeh, Sadeghnia, Tabarraei, & Sahebkar, ). In the previous study, we showed that EGCG increased apoptosis and inhibited telomerase activity in breast cancer cells (Moradzadeh, Sadeghnia, Tabarraei, & Sahebkar, ). In this study, we showed that EGCG decreased proliferation, induced apoptosis, and promoted differentiation in the promyelocytic leukemia cells via inhibition of MDR and PML‐RARα/HDAC1.…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin‐3‐gallate enhances differentiation of acute promyelocytic leukemia cells via inhibition of PML‐RARα and HDAC1

Moradzadeh

Roustazadeh

Tabarraei

et al. 2017

Phytotherapy Research

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The use of all-trans retinoic acid (ATRA) has dramatically improved the treatment and survival rate of patients with acute promyelocytic leukemia (APL). However, toxicity and resistance to this drug are major problems in the treatment of APL with ATRA. Earlier studies have suggested that the green tea polyphenol epigallocatechin gallate (EGCG) induces cell death in hematopoietic neoplasms without adversely affecting normal cells. In the present study, the potential therapeutic effect of EGCG in APL and the underlying molecular mechanisms were investigated. EGCG (100 μM) significantly inhibited proliferation and induced apoptosis in HL-60 and NB4 cells. This effect was associated with decreased expressions of multidrug resistance proteins ABCB1, and ABCC1, whereas the expressions of pro-apoptotic genes CASP3, CASP8, p21, and Bax/Bcl-2 ratio were significantly increased. EGCG, at 25 μM concentration, induced differentiation of leukemic cells towards granulocytic pattern in a similar manner to that observed for ATRA (1 μM). Furthermore, EGCG suppressed the expression of clinical marker PML/RARα in NB4 cells and reduced the expression of HDAC1 in leukemic cells. In conclusion, the results suggested that EGCG can be considered as a potential treatment for APL.

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“…Carotenes are vitamin A precursors and some xanthophylls such as L and Z are essential to prevent age-related macular degeneration ( Howitt and Pogson, 2006 ). Furthermore, carotenoids may have anti-cancer activity ( Moradzadeh et al, 2017 ) and some are used as food colorants, and added to cosmetics or pharmaceuticals. One of the few studies on the seeds of wild plant species revealed that grain legumes have lower contents of carotenoids (including those of nutritional value for human and livestock feeding, such as L and Z) than their wild counterparts, indicating a decrease in the concentration of carotenoids in seeds in the course of domestication ( Fernández-Marín et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Seed Carotenoid and Tocochromanol Composition of Wild Fabaceae Species Is Shaped by Phylogeny and Ecological Factors

et al. 2017

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Carotenoids distribution and function in seeds have been very scarcely studied, notwithstanding their pivotal roles in plants that include photosynthesis and phytohormone synthesis, pigmentation, membrane stabilization and antioxidant activity. Their relationship with tocochromanols, whose critical role in maintaining seed viability has already been evidenced, and with chlorophylls, whose retention in mature seed is thought to have negative effects on storability, remain also unexplored. Here, we aimed at elucidating seed carotenoids relationship with tocochromanols and chlorophylls with regard to phylogenetic and ecological traits and at understanding their changes during germination. The composition and distribution of carotenoids were investigated in seeds of a wide range of wild species across the Fabaceae (the second-most economically important family after the Poaceae). Photosynthetic pigments and tocochromanols were analyzed by HPLC in mature dry seeds of 50 species representative of 5 subfamilies within the Fabaceae (including taxa that represent all continents, biomes and life forms within the family) and at key timepoints during seedling establishment in three species representative of distinct clades. Total-carotenoids content positively correlated with tocopherols in the basal subfamilies Detarioideae, Cercidoideae, and Dialioideae, and with chlorophylls in the Papilionoideae. Papilionoideae lacked tocotrienols and had the highest total-carotenoids, chlorophyll and γ-tocopherol contents. Interestingly, lutein epoxide was present in 72% of the species including several herbs from different subfamilies. Overall, species original from temperate biomes presented higher carotenoids and lower tocochromanols levels than those from tropical biomes. Also shrub species showed higher carotenoids content than herbs and trees. During germination, total content of photosynthetic pigments increased in parallel to changes in relative abundance of carotenoids: zeaxanthin and anteraxanthin decreased and β-carotene augmented. Notably, the highest contents of nutritionally valuable carotenoids were found in Papilionoideae subfamily to which all pulses of socio-economic importance belong. The major differences in carotenoids and tocochromanols composition across the Fabaceae are apparently related to phylogeny in conjunction with ecological traits such as biome and growth form.

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Anti‐tumor effects of crocetin and related molecular targets

Cited by 42 publications

References 85 publications

Crocetin suppresses angiogenesis through inhibiting Sonic hedgehog signaling pathway in gastric cancer

Crocetin suppresses angiogenesis through inhibiting Sonic hedgehog signaling pathway in gastric cancer

Epigallocatechin‐3‐gallate enhances differentiation of acute promyelocytic leukemia cells via inhibition of PML‐RARα and HDAC1

Seed Carotenoid and Tocochromanol Composition of Wild Fabaceae Species Is Shaped by Phylogeny and Ecological Factors

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