Genistein: A Potent Anti-Breast Cancer Agent

Genistein is an isoflavonoid present in high quantities in soybeans. Possessing a wide range of bioactives, it is being studied extensively for its tumoricidal effects. Investigations into mechanisms of the anti-cancer activity have revealed many pathways including induction of cell proliferation, suppression of tyrosine kinases, regulation of Hedgehog-Gli1 signaling, modulation of epigenetic activities, seizing of cell cycle and Akt and MEK signaling pathways, among others via which the cancer cell proliferation can be controlled. Notwithstanding, the observed activities have been time- and dose-dependent. In addition, genistein has also shown varying results in women depending on the physiological parameters, such as the early or post-menopausal states.

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Anti-cancer activity of NVP-TAE226, a potent dual FAK/IGF-IR kinase inhibitor, against pancreatic carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13162 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13162-13162 ◽

Cited By ~ 3

Author(s):

S. Hatakeyama ◽

D. Tomioka ◽

E. Kawahara ◽

N. Matsuura ◽

K. Masuya ◽

...

Keyword(s):

Cell Proliferation ◽

Pancreatic Carcinoma ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Proliferation ◽

Normal Cells ◽

P Glycoprotein ◽

Anti Cancer ◽

Cancer Activity

13162 Background: Focal adhesion kinase (FAK) is a non-receptor cytoplasmic tyrosine kinase that regulates multiple cell functions. Elevated expression levels of FAK have been detected in various tumor samples and are closely correlated with invasive potential. Activation of integrins and the growth factor receptors result in FAK autophosphorylation at Y397 and the presentation of suitable binding sites for proteins containing either SH2 or phosphotyrosine binding domains. Recent evidences suggest that FAK plays important roles in cancer cell proliferation and survival. IGF-IR function is required for tumor cell survival, but dispensable for survival of normal cells. Therefore, a dual inhibitor of both kinases may selectively block the growth, migration, and survival of FAK- and IGF-IR- expressing tumor cells compared to proliferating and migrating normal cells. Methods: In this study, anti-cancer activity of NVP-TAE226 that is identified as a potent and selective FAK inhibitor was evaluated in cancer cell lines panel and MIA PaCa-2 pancreatic carcinoma in vivo model. Results: Mean GI50 value of NVP-TAE226 against 37 cancer cell lines was 0.76 μmole/L. Inhibition of cancer cell proliferation was not affected by expression of P-glycoprotein, suggesting that NVP-TAE226 is not served as a substrate of P-glycoprotein. Oral administration of NVP-TAE226 efficiently inhibited MIA PaCa-2 human pancreatic tumor growth at all doses tested. Tumor stasis was observed at a dose of 30 mg/kg, qd for 7×/week and tumor regression was observed at a dose of 100 mg/kg, qd for 5×/week. All animals tolerated NVP-TAE226 treatment up to 100 mg/kg, 5×/wk, qd, po for 2 weeks with no body weight loss. Inhibition of downstream signaling such as phosphorylation of Akt at Serine473 was accompanied by inhibition of FAK phosphorylation in human pancreatic carcinoma cell lines. Conclusions: NVP-TAE226 is a novel class of selective and small molecule kinase inhibitors with a potent in vivo activity and potential therapeutic application. No significant financial relationships to disclose.

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Anti-cancer activity of Tonglian decoction against esophageal cancer cell proliferation through regulation of the cell cycle and PI3K/Akt signaling pathway

Journal of Traditional Chinese Medical Sciences ◽

10.1016/j.jtcms.2016.01.007 ◽

2015 ◽

Vol 2 (2) ◽

pp. 120-126

Author(s):

Yongsen Jia ◽

Lijuan Qin ◽

Chunhua Jiang ◽

Qing Lin ◽

Fuling Tian ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Esophageal Cancer ◽

Cancer Cell ◽

Akt Signaling ◽

Cancer Cell Proliferation ◽

Akt Signaling Pathway ◽

Anti Cancer ◽

Esophageal Cancer Cell ◽

Cancer Activity

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Two Cu(II) co-ordination polymers: anti-cancer activity on melanoma by reducing cancer cell proliferation, migration, and invasion ability

Inorganic and Nano-Metal Chemistry ◽

10.1080/24701556.2020.1783314 ◽

2020 ◽

Vol 51 (2) ◽

pp. 239-245

Author(s):

Zhaopeng Xuan ◽

Yamei Zhan ◽

Guangyun Song ◽

Bin Liu

Keyword(s):

Cell Proliferation ◽

Cancer Cell ◽

Migration And Invasion ◽

Cancer Cell Proliferation ◽

Anti Cancer ◽

Cancer Activity

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Sulforaphane induces colorectal cancer cell proliferation through Nrf2 activation in a p53-dependent manner

Applied Biological Chemistry ◽

10.1186/s13765-020-00578-y ◽

2020 ◽

Vol 63 (1) ◽

Author(s):

Yunjeong Gwon ◽

Jisun Oh ◽

Jong-Sang Kim

Keyword(s):

Colon Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cancer Cell ◽

Related Factor ◽

Mild Stress ◽

Dependent Manner ◽

Cancer Cell Proliferation ◽

Nrf2 Signaling Pathway ◽

Dose Dependent

AbstractSulforaphane is a well-known phytochemical that stimulates nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant cellular response. In this study, we found that sulforaphane promoted cell proliferation in HCT116 human colon cancer cells expressing a normal p53 gene in a dose-dependent but biphasic manner. Since p53 has been reported to contribute to cell survival by regulating various metabolic pathways to adapt to mild stress, we further examined cellular responses in both p53-wild-type (WT) and p53-knockout (KO) HCT116 cells exposed to sulforaphane in vitro and in vivo. Results demonstrated that sulforaphane treatment activated Nrf2-mediated antioxidant enzymes in both p53-WT and p53-KO cells, decreased apoptotic protein expression in WT cells but increased in KO cells in a dose-dependent manner, and increased the expression of a mitochondrial biogenesis marker PGC1α in WT cells but decreased in KO cells. Moreover, a low dose of sulforaphane promoted tumor growth, upregulated the Nrf2 signaling pathway, and decreased apoptotic cell death in p53-WT HCT116 xenografts compared to that in p53-KO HCT116 xenografts in BALB/c nude mice. These findings suggest that sulforaphane can influence colon cancer cell proliferation and mitochondrial function through a crosstalk between the Nrf2 signaling pathway and p53 axis.

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New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene

Molecules ◽

10.3390/molecules26133888 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3888

Author(s):

Boon-Peng Puah ◽

Juriyati Jalil ◽

Ali Attiq ◽

Yusof Kamisah

Keyword(s):

Immune Cells ◽

Scientific Evidence ◽

Special Role ◽

Real Potential ◽

Wide Range ◽

Anti Cancer ◽

The Family ◽

The Relationship ◽

Cancer Activity ◽

Reduced Risk

Lycopene is a well-known compound found commonly in tomatoes which brings wide range of health benefits against cardiovascular diseases and cancers. From an anti-cancer perspective, lycopene is often associated with reduced risk of prostate cancer and people often look for it as a dietary supplement which may help to prevent cancer. Previous scientific evidence exhibited that the anti-cancer activity of lycopene relies on its ability to suppress oncogene expressions and induce proapoptotic pathways. To further explore the real potential of lycopene in cancer prevention, this review discusses the new insights and perspectives on the anti-cancer activities of lycopene which could help to drive new direction for research. The relationship between inflammation and cancer is being highlighted, whereby lycopene suppresses cancer via resolution of inflammation are also discussed herein. The immune system was found to be a part of the anti-cancer system of lycopene as it modulates immune cells to suppress tumor growth and progression. Lycopene, which is under the family of carotenoids, was found to play special role in suppressing lung cancer.

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Clinical significance of activated Wnt/β-catenin signaling in apoptosis inhibition of oral cancer

Open Life Sciences ◽

10.1515/biol-2021-0104 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1045-1052

Author(s):

Yufeng Wang ◽

Zheng Cao ◽

Fengjia Liu ◽

Yuejian Ou

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Apoptotic Cell ◽

Cancer Cell Proliferation ◽

Rt Pcr ◽

Sirna Transfection ◽

Apoptosis Resistance ◽

Apoptosis Inhibition ◽

Anti Cancer ◽

Evolutionarily Conserved

Abstract Wnt/β‐catenin signaling is an evolutionarily conserved pathway and plays a crucial role in regulating cancer cell proliferation and tumorigenesis. However, the molecular mechanism behind the Wnt/β‐catenin signaling-mediated carcinogenesis and apoptosis resistance in oral squamous cell carcinoma is not well characterized so far. In the present study, we have investigated the effect of β‐catenin depletion of the perversely activated Wnt/β-catenin signaling pathway on apoptosis resistance and tumorigenesis of the human OSCC cell line SCC-55. RT-PCR and western blot analysis demonstrated that the Wnt/β-catenin signaling pathway and its downstream targets such as DKK1 and AXIN2 are aberrantly activated in SCC-55 cells. Furthermore, upon silencing (RNA interference) of β‐catenin in SCC-55, cells became more sensitive toward the chemotherapeutic drugs and thus resulted in apoptotic cell death. Meanwhile, flow cytometry analysis confirmed the enhanced apoptosis and activation of caspases in β‐catenin RNAi cells. Besides ensuing β-catenin–siRNA transfection, the cell proliferation and cancer colony generating efficiencies are significantly impeded compared to the non-transfected cells. Furthermore, the tumorigenicity was inhibited by the downregulation of OCT-4 in β‐catenin-silenced SCC-55 cells. Altogether, Wnt/β‐catenin signaling could potentially target anti-cancer drugs to induce apoptosis and achieve a better clinical outcome.

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Breast Cancer Therapeutics Based on Fusarochromanone and EGFR Inhibitors

10.21203/rs.3.rs-289662/v1 ◽

2021 ◽

Author(s):

Natalie Carroll ◽

Alena Smith ◽

Brian A. Salvatore ◽

Elahe Mahdavian

Keyword(s):

Breast Cancer ◽

Mode Of Action ◽

Cancer Therapeutics ◽

Egfr Inhibitors ◽

Cancer Therapies ◽

Racemic Form ◽

Combination Treatments ◽

Anti Cancer ◽

Cancer Agent ◽

Cancer Activity

Abstract Background: Fusarochromanone (FC101) is a small molecule with potent anti-cancer activity. It was originally derived from the fungal plant pathogen, Fusarium equiseti, and it has also been synthesized in non-racemic form in our lab. Numerous studies reveal the promising biological activity of FC101, including potent anti-angiogenic and anti-cancer activity. While FC101 is potent as a single drug treatment across many cancer cell lines, current cancer therapies often incorporate a combination of drugs in order to increase efficacy and decrease the development of drug resistance. In this study, we leverage drug combinations and cellular phenotypic screens to address important questions about FC101’s mode of action and its potential synergies as an anti-cancer therapeutic agent in triple negative breast cancer (TNBC).Method: We hypothesized that FC101’s activity against TNBC is similar to the known mTOR inhibitor, everolimus, because FC101 reduces the phosphorylation of two key mTOR substrates, S6K and S6. Since everolimus synergistically enhances the anti-cancer activities of known EGFR inhibitors (erlotinib or lapatinib) in TNBC, we performed analogous studies with FC101. Phenotypic cellular assays helped assess whether FC101 (in both single and combination treatments) acts similarly to everolimus.Results: FC101 outperformed all other single treatments in both cell proliferation and viability assays. Unlike everolimus, however, FC101 brought about a sustained decrease in cell viability in drug washout studies. None of the other drugs were able to maintain comparable effects upon removal of the treatment agents. Although we observed slightly additive effects when the TNBC cells were treated with FC101 and either EGFR inhibitor, those effects were not truly synergistic in the manner displayed with everolimus. Conclusion: Our results rule out direct inhibition of mTOR by FC101 and suggest that FC101 acts through a different mechanism than everolimus. This lays the foundation for the refinement of our hypothesis in order to better understand FC101’s mode of action as a novel anti-cancer agent.

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The Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid Is a CDK Inhibitor and an Anti-Proliferative Agent: A Potential Role in Cancer Prevention

Cancers ◽

10.3390/cancers11030427 ◽

2019 ◽

Vol 11 (3) ◽

pp. 427 ◽

Cited By ~ 20

Author(s):

Ranjini Sankaranarayanan ◽

Chaitanya Valiveti ◽

D. Kumar ◽

Severine Van slambrouck ◽

Siddharth Kesharwani ◽

...

Keyword(s):

Cell Proliferation ◽

Cancer Cell Proliferation ◽

Cyclin Dependent Kinase ◽

Specific Amino Acid ◽

In Silico Studies ◽

Anti Cancer ◽

Anti Oxidant ◽

First Time ◽

Related Compounds

Flavonoids have emerged as promising compounds capable of preventing colorectal cancer (CRC) due to their anti-oxidant and anti-inflammatory properties. It is hypothesized that the metabolites of flavonoids are primarily responsible for the observed anti-cancer effects owing to the unstable nature of the parent compounds and their degradation by colonic microflora. In this study, we investigated the ability of one metabolite, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) to inhibit Cyclin Dependent Kinase (CDK) activity and cancer cell proliferation. Using in vitro kinase assays, we demonstrated that 2,4,6-THBA dose-dependently inhibited CDKs 1, 2 and 4 and in silico studies identified key amino acids involved in these interactions. Interestingly, no significant CDK inhibition was observed with the structurally related compounds 3,4,5-trihydroxybenzoic acid (3,4,5-THBA) and phloroglucinol, suggesting that orientation of the functional groups and specific amino acid interactions may play a role in inhibition. We showed that cellular uptake of 2,4,6-THBA required the expression of functional SLC5A8, a monocarboxylic acid transporter. Consistent with this, in cells expressing functional SLC5A8, 2,4,6-THBA induced CDK inhibitory proteins p21Cip1 and p27Kip1 and inhibited cell proliferation. These findings, for the first time, suggest that the flavonoid metabolite 2,4,6-THBA may mediate its effects through a CDK- and SLC5A8-dependent pathway contributing to the prevention of CRC.

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