Genistein combined with FOLFOX or FOLFOX–Bevacizumab for the treatment of metastatic colorectal cancer: phase I/II pilot study

Pintova, Sofya; Dharmupari, Sirish; Moshier, Erin; Zubizarreta, Nicole; Ang, Celina; Holcombe, Randall F.

doi:10.1007/s00280-019-03886-3

Cited by 91 publications

(57 citation statements)

References 23 publications

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“…Therefore, Pintova et al evaluated the safety of genistein combined with standard fluoropyrimidine and platinum-based chemotherapy in the treatment of metastatic colorectal cancer in a phase I/II pilot study. After all, genistein added to FOLFOX or FOLFOX-Bevacizumav was demonstrated to be safe and tolerable [ 116 ]. In addition, the bioavailability of EGCG was also improved by the use of Greenselect Phytosome (GSP), a lecithin formulation of a caffeine-free green tea catechin extract, in early breast cancer patients receiving 300 mg of GSP, an equivalent to 44.9 mg of EGCG daily for 4 weeks prior to surgery [ 117 ].…”

Section: Targeting Metastatic Cancermentioning

confidence: 99%

Flavonoids in Cancer Metastasis

Líšková

Koklesová

Samec

et al. 2020

Cancers

137

128

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Metastasis represents a serious complication in the treatment of cancer. Flavonoids are plant secondary metabolites exerting various health beneficiary effects. The effects of flavonoids against cancer are associated not only with early stages of the cancer process, but also with cancer progression and spread into distant sites. Flavonoids showed potent anti-cancer effects against various cancer models in vitro and in vivo, mediated via regulation of key signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of epithelial-mesenchymal transition or regulatory molecules such as MMPs, uPA/uPAR, TGF-β and other contributors of the complex process of metastatic spread. Moreover, flavonoids modulated also the expression of genes associated with the progression of cancer and improved inflammatory status, a part of the complex process involved in the development of metastasis. Flavonoids also documented clear potential to improve the anti-cancer effectiveness of conventional chemotherapeutic agents. Most importantly, flavonoids represent environmentally-friendly and cost-effective substances; moreover, a wide spectrum of different flavonoids demonstrated safety and minimal side effects during long-termed administration. In addition, the bioavailability of flavonoids can be improved by their conjugation with metal ions or structural modifications by radiation. In conclusion, anti-cancer effects of flavonoids, targeting all phases of carcinogenesis including metastatic progression, should be implemented into clinical cancer research in order to strengthen their potential use in the future targeted prevention and therapy of cancer in high-risk individuals or patients with aggressive cancer disease with metastatic potential.

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Section: Targeting Metastatic Cancermentioning

confidence: 99%

Flavonoids in Cancer Metastasis

Líšková

Koklesová

Samec

et al. 2020

Cancers

137

128

View full text Add to dashboard Cite

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“…The cytotoxic activity of genistein was previously determined by inhibiting the intracellular signal transduction pathway that support and potentiate cell proliferation and growth as well as promoting the angiogenesis process [27]. The activity of genistein against Hela cell line may be due to inhibition of the expression of VEGF and VEGF receptors and Down-regulation of the expression of miR-27a which lead to induction of cell cycle arrest [26].…”

Section: Discussionmentioning

confidence: 99%

New Insights into cytotoxic metabolites produced by Streptomyces griseus isolate KJ623766: Large scale production, structure elucidation and biological activities

Abu‐Zaid

Aleissawy

Aboshanab

et al. 2019

Preprint

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Natural products particularly microbial metabolites have been the mainstay of cancer chemotherapy and are likely to provide many of the lead structures and derivatives with new biological activities. In this research, the production of some potential cytotoxic metabolites from Streptomyces (S.) griseus isolate KJ623766 was carried out in 1 4 L laboratory fermenter under specified optimum conditions (28°C temperature, 200 RPM rotation speed, uncontrolled PH, 3 vvm aeration and 2 bar airflow pressure). Using 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide (MTT) assay, the cytotoxic activity of the ethyl acetate (1:1, v/v) extract of cell free culture supernatant (CFCS) against Caco2 and Hela cancer cell lines was determined with CD 50 of 14 µg/ml and 20 µg/ml, respectively. Bioassay guided fractionation of the ethyl acetate extract using different chromatographic techniques had led to the purification of the cytotoxic metabolites coded W1, R1 and R2 with reproducible amounts of 20, 5, and 1.5 mg/l, respectively. The structures of respective metabolites were determined using various spectroscopic analysis and identified as genistein, β-rhodomycinone and γ- rhodomycinone, respectively. Accordingly, S. griseus isolate KJ623766 can be used as a potential industrial strain for the large scale production of the isoflavonoid genistein, as well as for the production of β-and γ- rhodomycinone to be used for the construction of new derivatives with more potent cytotoxic activities of the anthracycline family. This is the first report about the production of the isoflavonoid genistein by S. griseus KJ623766.

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“…The cytotoxic activity of genistein has been shown to be due to targeting the PI 3 K/Akt pathway. Downstream, genistein inhibits EGF induced FOXO3 disassociation from p53 (mut), which further promotes FOXO3 activity and leads to increased expression of the p27kip1 cell cycle inhibitor, which inhibits proliferation in colon cancer cells [27]. The activity of genistein against Hela cell line may be due to inhibition of the expression of VEGF and VEGF receptors and Down-regulation of the expression of miR-27a which lead to induction of cell cycle arrest [26].…”

Section: Discussionmentioning

confidence: 99%

New Insights into cytotoxic metabolites produced by Streptomyces griseus isolate KJ623766: Large scale production, structure elucidation and biological activities

Zaid

Aleissawy

Aboshanab

et al. 2019

Preprint

View full text Add to dashboard Cite

Natural products particularly microbial metabolites have been the mainstay of cancer chemotherapy and are likely to provide many of the lead structures and derivatives with new biological activities. In this research, the production of some potential cytotoxic metabolites from Streptomyces (S.) griseus isolate KJ623766 was carried out in 14 L laboratory fermenter under specified optimum conditions (28°C temperature, 200 RPM rotation speed, uncontrolled PH, 3 vvm aeration and 2 bar airflow pressure). After 72 hrs of incubation, the cell free culture supernatant (CFCS) was collected and extracted using ethyl acetate (1:1, v/v) at pH 7.0. Using 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide (MTT) assay, the cytotoxic activity of the ethyl acetate extract against Caco2 and Hela cancer cell lines was determined with CD50 of 14 µg/ml and 20 µg/ml, respectively. Bioassay guided fractionation of the ethyl acetate extract using different chromatographic techniques had led to the purification of the cytotoxic metabolites coded W1, R1 and R2 with reproducible amounts of 20, 5, and 1.5 mg/l, respectively. The structures of respective metabolites were determined based on the mass, 1D and 2D NMR spectroscopic analysis and were identified as genistein, β-rhodomycinone and γ- rhodomycinone, respectively. Accordingly, S. griseus isolate KJ623766 can be used as a potential industrial strain for the commercial production of the isoflavonoid genistein, as well as for the production of β-and γ- rhodomycinone to be used for the construction of new derivatives with more potent cytotoxic activities of the anthracycline family. To the best of our knowledge, this is the first report about the production of the isoflavonoid genistein by S. griseus KJ623766.

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Genistein combined with FOLFOX or FOLFOX–Bevacizumab for the treatment of metastatic colorectal cancer: phase I/II pilot study

Cited by 91 publications

References 23 publications

Flavonoids in Cancer Metastasis

Flavonoids in Cancer Metastasis

New Insights into cytotoxic metabolites produced by Streptomyces griseus isolate KJ623766: Large scale production, structure elucidation and biological activities

New Insights into cytotoxic metabolites produced by Streptomyces griseus isolate KJ623766: Large scale production, structure elucidation and biological activities

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