Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies

Farahi, Ali; Abedini, Mohammad Reza; Javdani, Hossein; Arzi, Laleh; Chamani, Elham; Farhoudi, Ramin; Talebloo, Nazanin; Hoshyar, Reyhane

doi:10.1007/s11010-020-04043-8

Cited by 20 publications

(7 citation statements)

References 40 publications

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“…These results demonstrated that crocin inhibited VEGF secretion by colon carcinoma cells in a concentration dependent manner. It was in agreement with the findings of Farahi et al, who revealed the potential for a combination therapy of metformin and crocin to suppress VEGF in breast cancer metastasis [51].…”

Section: Discussionsupporting

confidence: 93%

Crocin Inhibits Angiogenesis and Metastasis in Colon Cancer via TNF-α/NF-kB/VEGF Pathways

Bakshi

Quinn

Nasef

et al. 2022

Cells

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Angiogenesis and metastasis play pivotal roles in the progression of cancer. We recently discovered that crocin, a dietary carotenoid derived from the Himalayan crocus, inhibited the growth of colon cancer cells. However, the exact role of crocin on the angiogenesis and metastasis in colorectal cancer remains unclear. In the present study, we demonstrated that crocin significantly reduces the viability of colon cancer cells (HT-29, Caco-2) and human umbilical vein endothelial cells (HUVEC), but was not toxic to human colon epithelial (HCEC) cells. Furthermore, pre-treatment of human carcinoma cells (HT-29 and Caco-2) with crocin inhibited cell migration, invasion, and angiogenesis in concentration -dependent manner. Further studies demonstrated that crocin inhibited TNF-α, NF-κB and VEGF pathways in colon carcinoma cell angiogenesis and metastasis. Crocin also inhibited cell migration, invasion, and tube formation in human umbilical vein endothelial cells (HUVEC) in a concentration -dependent manner. We also observed that crocin significantly reduced the secretion of VEGF and TNF-α induced activation of NF-kB by human colon carcinoma cells. In the absence of TNF-α, a concentration-dependent reduction in NF-kB was observed. Many of these observations were confirmed by in vivo angiogenesis models, which showed that crocin significantly reduced the progression of tumour growth. Collectively, these finding suggest that crocin inhibits angiogenesis and colorectal cancer cell metastasis by targeting NF-kB and blocking TNF-α/NF-κB/VEGF pathways.

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Section: Discussionsupporting

confidence: 93%

Crocin Inhibits Angiogenesis and Metastasis in Colon Cancer via TNF-α/NF-kB/VEGF Pathways

Bakshi

Quinn

Nasef

et al. 2022

Cells

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“…Furthermore, TNF-α was shown to induce the epithelial-to-mesenchymal transition in Human HCC cell lines [ 76 ]. It is noteworthy that high TNF-α expression levels were correlated with poor outcomes in HCC patients who received post-surgery adjuvant sorafenib [ 77 ]. This was explained by resistance to the sorafenib treatment.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights

et al. 2022

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This study investigated the therapeutic effects of the phytochemical crocin alone or in combination with sorafenib both in rats chemically induced with hepatocellular carcinoma (HCC) and in human liver cancer cell line (HepG2). Male rats were randomly divided into five groups, namely, control group, HCC induced group, and groups treated with sorafenib, crocin or both crocin and sorafenib. HCC was induced in rats with a single intraperitoneal injection of diethylnitrosamine (DEN), then 2-acetylaminofluorene (2-AAF). The HCC-induced rats showed a significant decrease in body weight compared to animals treated with either or both examined drugs. Serum inflammatory markers (C-reactive protein (CRP); interleukin-6 (IL-6); lactate dehydrogenase (LDH), and oxidative stress markers were significantly increased in the HCC group and were restored upon treatment with either or both of therapeutic molecules. Morphologically, the HCC-induced rats manifested most histopathological features of liver cancer. Treatment with either or both of crocin and sorafenib successfully restored normal liver architecture. The expression of key genes involved in carcinogenesis (TNFα, p53, VEGF and NF-κB) was highly augmented upon HCC induction and was attenuated post-treatment with either or both examined drugs. Treatment with both crocin and sorafenib improved the histopathological and inflammation parameters as compared to single treatments. The in vivo anti-cancer effects of crocin and/or sorafenib were supported by their respective cytotoxicity on HepG2 cells. Crocin and sorafenib displayed an anti-tumor synergetic effect on HepG2 cells. The present findings demonstrated that a treatment regimen with crocin and sorafenib reduced liver toxicity, impeded HCC development, and improved the liver functions.

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“…Zhao et al (2021) with in vitro and in vivo studies demonstrated the angiogenesis inhibitory effect of crocin exerted through VEGF signaling pathway inhibition. Crocin inhibited VEGF expression and may be helpful as an attractive alternative option for cancer treatment, including breast cancer (Farahi et al, 2021; Saravani et al, 2020) and melanoma (Bakshi et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Crocin molecular signaling pathways at a glance: A comprehensive review

Boozari

Rahbardar

2022

Phytotherapy Research

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Crocin is a hydrophilic carotenoid that is synthesized in the flowers of the Crocus genus. Numerous in vitro and in vivo research projects have been published about the biological and pharmacological properties and toxicity of crocin. Crocin acts as a memory enhancer, anxiolytic, aphrodisiac, antidepressant, neuroprotective, and so on. Here, we introduce an updated and comprehensive review of crocin molecular mechanisms based on previously examined and mentioned in the literature. Different studies confirmed the significant effect of crocin to control pathological conditions, including oxidative stress, inflammation, metabolic disorders, neurodegenerative disorders, and cancer. The neuroprotective effect of crocin could be related to the activation of phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT)/mammalian target of rapamycin (mTOR), Notch, and cyclic‐AMP response element‐binding protein signaling pathways. The crocin also protects the cardiovascular system through the inhibitory effect on toll‐like receptors. The regulatory effect of crocin on PI3K/AKT/mTOR, AMP‐activated protein kinase, mitogen‐activated protein kinases (MAPK), and peroxisome proliferator‐activated receptor pathways can play an effective role in the treatment of metabolic disorders. The crocin has anticancer activity through the PI3K/AKT/mTOR, MAPK, vascular endothelial growth factor, Wnt/β‐catenin, and Janus kinases‐signal transducer and activator of transcription suppression. Also, the nuclear factor‐erythroid factor 2‐related factor 2 and p53 signaling pathway activation may be effective in the anticancer effect of crocin. Finally, among signaling pathways regulated by crocin, the most important ones seem to be those related to the regulatory effect on the PI3K/AKT/mTOR pathway.

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Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies

Cited by 20 publications

References 40 publications

Crocin Inhibits Angiogenesis and Metastasis in Colon Cancer via TNF-α/NF-kB/VEGF Pathways

Crocin Inhibits Angiogenesis and Metastasis in Colon Cancer via TNF-α/NF-kB/VEGF Pathways

Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights

Crocin molecular signaling pathways at a glance: A comprehensive review

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