Curcumin analogue GO-Y030 inhibits STAT3 activity and cell growth in breast and pancreatic carcinomas

Hutzen, Brian; Friedman, Lauren; Sobo, Matthew; Li, Lin; Cen, Ling; Angelis, Stephanie De; Yamakoshi, Hiroyuki; Shibata, Hiroyuki; Iwabuchi, Yoshiharu; Lin, Jiayuh

doi:10.3892/ijo_00000401

Cited by 31 publications

(4 citation statements)

References 23 publications

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“…Indeed, curcumin treatment exhibited potent growth suppressive activity and repressed the STAT3 phosphorylation in the MDA-MB-231 and SKBR-3. This result was further confirmed through the inhibitory effect of curcumin on the DNA binding capability of STAT3 and its transcriptional activity [ 76 ], which were in accordance with previous reports [ 67 , 77 ]. Therefore, curcumin targets STAT3 signaling by blocking STAT3 activation in vitro.…”

Section: Curcumin: Impacts On Multiple Cellular Signaling Pathways In Hormone-independent Breast Cancersupporting

confidence: 90%

Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

Farghadani

Naidu

2021

Cancers

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Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Despite the overall successes in breast cancer therapy, hormone-independent HER2 negative breast cancer, also known as triple negative breast cancer (TNBC), lacking estrogens and progesterone receptors and with an excessive expression of human epidermal growth factor receptor 2 (HER2), along with the hormone-independent HER2 positive subtype, still remain major challenges in breast cancer treatment. Due to their poor prognoses, aggressive phenotype, and highly metastasis features, new alternative therapies have become an urgent clinical need. One of the most noteworthy phytochemicals, curcumin, has attracted enormous attention as a promising drug candidate in breast cancer prevention and treatment due to its multi-targeting effect. Curcumin interrupts major stages of tumorigenesis including cell proliferation, survival, angiogenesis, and metastasis in hormone-independent breast cancer through the modulation of multiple signaling pathways. The current review has highlighted the anticancer activity of curcumin in hormone-independent breast cancer via focusing on its impact on key signaling pathways including the PI3K/Akt/mTOR pathway, JAK/STAT pathway, MAPK pathway, NF-ĸB pathway, p53 pathway, and Wnt/β-catenin, as well as apoptotic and cell cycle pathways. Besides, its therapeutic implications in clinical trials are here presented.

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Section: Curcumin: Impacts On Multiple Cellular Signaling Pathways In Hormone-independent Breast Cancersupporting

confidence: 90%

Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

Farghadani

Naidu

2021

Cancers

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“…GO-Y030 induces apoptosis in multiple tumor cells by inhibiting the activation of STAT3 (45). We confirmed that GO-Y030treatment strongly reduced the survival of B16-F10 melanoma cells (Figures 5A, B) and STAT3 activation (Figures 5C, D) compared with curcumin treatment.…”

Section: Go-y030 Controls Antitumor Immunitysupporting

confidence: 75%

The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells

et al. 2021

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Regulatory T cells (Tregs) play a crucial role in preventing antitumor immune responses in cancer tissues. Cancer tissues produce large amounts of transforming growth factor beta (TGF-β), which promotes the generation of Foxp3+ Tregs from naïve CD4+ T cells in the local tumor microenvironment. TGF-β activates nuclear factor kappa B (NF-κB)/p300 and SMAD signaling, which increases the number of acetylated histones at the Foxp3 locus and induces Foxp3 gene expression. TGF-β also helps stabilize Foxp3 expression. The curcumin analog and antitumor agent, GO-Y030, prevented the TGF-β-induced generation of Tregs by preventing p300 from accelerating NF-κB-induced Foxp3 expression. Moreover, the addition of GO-Y030 resulted in a significant reduction in the number of acetylated histones at the Foxp3 promoter and at the conserved noncoding sequence 1 regions that are generated in response to TGF-β. In vivo tumor models demonstrated that GO-Y030-treatment prevented tumor growth and reduced the Foxp3+ Tregs population in tumor-infiltrating lymphocytes. Therefore, GO-Y030 exerts a potent anticancer effect by controlling Treg generation and stability.

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“…Similarly, previous studies also observed that colon, pancreatic, and gastric cancer cells treated with FLLL-11 [ 15 , 25 ] and GO-Y022 [ 26 ], which has identical structure as MS13 showed lower IC 50 values compared to curcumin by several fold. In addition, other DAPs such as HO-3867 [ 16 , 27 ], EF24 [ 17 , 28 ], and GO-Y030 [ 29 , 30 ] demonstrated reduction in cell viability of human lung cancer cells compared to curcumin. It was also observed that NCI-H23 cells exhibited lower EC 50 values compared to NCI-H520 cells following MS13 treatment.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of Antiproliferative and Apoptosis Activity by 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)1,4-Pentadiene-3-one (MS13) on Human Non-Small Cell Lung Cancer Cells

Tajuddin

Abas

Othman

et al. 2021

IJMS

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Diarylpentanoid (DAP), an analog that was structurally modified from a naturally occurring curcumin, has shown to enhance anticancer efficacy compared to its parent compound in various cancers. This study aims to determine the cytotoxicity, antiproliferative, and apoptotic activity of diarylpentanoid MS13 on two subtypes of non-small cell lung cancer (NSCLC) cells: squamous cell carcinoma (NCI-H520) and adenocarcinoma (NCI-H23). Gene expression analysis was performed using Nanostring PanCancer Pathways Panel to determine significant signaling pathways and targeted genes in these treated cells. Cytotoxicity screening revealed that MS13 exhibited greater inhibitory effect in NCI-H520 and NCI-H23 cells compared to curcumin. MS13 induced anti-proliferative activity in both cells in a dose- and time-dependent manner. Morphological analysis revealed that a significant number of MS13-treated cells exhibited apoptosis. A significant increase in caspase-3 activity and decrease in Bcl-2 protein concentration was noted in both MS13-treated cells in a time- and dose-dependent manner. A total of 77 and 47 differential expressed genes (DEGs) were regulated in MS13 treated-NCI-H520 and NCI-H23 cells, respectively. Among the DEGs, 22 were mutually expressed in both NCI-H520 and NCI-H23 cells in response to MS13 treatment. The top DEGs modulated by MS13 in NCI-H520—DUSP4, CDKN1A, GADD45G, NGFR, and EPHA2—and NCI-H23 cells—HGF, MET, COL5A2, MCM7, and GNG4—were highly associated with PI3K, cell cycle-apoptosis, and MAPK signaling pathways. In conclusion, MS13 may induce antiproliferation and apoptosis activity in squamous cell carcinoma and adenocarcinoma of NSCLC cells by modulating DEGs associated with PI3K-AKT, cell cycle-apoptosis, and MAPK pathways. Therefore, our present findings could provide an insight into the anticancer activity of MS13 and merits further investigation as a potential anticancer agent for NSCLC cancer therapy.

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Curcumin analogue GO-Y030 inhibits STAT3 activity and cell growth in breast and pancreatic carcinomas

Cited by 31 publications

References 23 publications

Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells

Molecular Mechanisms of Antiproliferative and Apoptosis Activity by 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)1,4-Pentadiene-3-one (MS13) on Human Non-Small Cell Lung Cancer Cells

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