Curcumol enhances the anti-tumor effects of metformin via suppressing epithelial-mesenchymal transition in triple-negative breast cancer

Wang, Gangyue; Dong, Yi; Liu, Heng

doi:10.21037/atm-20-5438

Cited by 16 publications

(9 citation statements)

References 49 publications

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“…As shown in our present study, curcumol inhibits MDR in CRC. Consistent with our results, curcumol has been reported to inhibit Wnt/β-catenin signaling in triple-negative breast cancer and lung adenocarcinoma ( 53 , 54 ). Importantly, aberrant Wnt/β-catenin signaling plays a critical role in the development and progression of various human malignancies, and mutations in this pathway’s components are defining CRC features ( 30 , 55 ).…”

Section: Discussionsupporting

confidence: 92%

Curcumol increases the sensitivity of colon cancer to 5-FU by regulating Wnt/β-catenin signaling

Gao¹,

Hou²,

Hu³

et al. 2021

Transl Cancer Res TCR

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Background: 5-fluorouracil (5-FU) resistance is the leading cause of treatment failure in colon cancer.Combination therapy is an effective strategy to inhibit cancer cells and prevent drug resistance. Therefore, we studied the antitumor effect of curcumol alone or combined with 5-FU on human colon cancer drugresistant cells. Methods:The 5-FU resistant HCT116 cell line (HCT116/5-FU) was established by repeated exposure to gradually increasing concentrations of 5-FU; Cell viability was measured by cell counting kit-8 (CCK-8); apoptosis rate of HCT116 cells was detected using Annexin V-fluorescein isothiocyanate (FITC) assay kit; cell proliferation and invasion were detected using colony formation assays, wound healing assay and transwell invasion assays; activity of transplanted tumor in vivo in specific pathogen free (SPF) BALB/c nude mice (6 weeks old, male) was monitored by bioluminescence imaging, immunohistochemistry and western blot analysis.Results: Our study showed the potent antitumor effect of curcumol by induction of apoptosis, inhibition of proliferation, invasion, migration, and improvement of the therapeutic efficacy of 5-FU toward human colon cancer HCT116 cells. From our results, curcumol could chemosensitize 5-FU-resistant HCT116 cells. The combination of curcumol and 5-FU exerted a synergistic inhibitory effect on the induction of apoptosis. Also, this combination inhibited the proliferation, invasion, and migration of both chemo-resistant and sensitive cells. Curcumol treatment decreased multidrug resistance-associated protein 2 (MRP-2), P-glycoprotein (P-gp), survivin, and β-catenin expression, which correlated with multidrug resistance (MDR) and the target genes of Wnt/β-catenin. It significantly increased the p-β-catenin level and Bad/Bcl-2 ratio in HCT116/5-FU cells compared with 5-FU treatment. In vivo, curcumol significantly inhibited the growth of transplanted tumors and the expression of Ki-67, proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF) in colon cancer cells.Conclusions: Curcumol as a potential chemotherapeutic agent combined with 5-FU can overcome colon cancer resistance.

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Section: Discussionsupporting

confidence: 92%

Curcumol increases the sensitivity of colon cancer to 5-FU by regulating Wnt/β-catenin signaling

Gao¹,

Hou²,

Hu³

et al. 2021

Transl Cancer Res TCR

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“… 12 The fibrosis mediated by fibroblasts originating from endothelial cells contributes to the pathological process of DCM, as has been reported previously. 11 The inhibition for EndMT/EMT by metformin has been reported in several studies, 35 , 36 while the action by SGLT2 inhibitors is still unclear. Our study represents the first to investigate how dapagliflozin affects EndMT and fibroblasts and to thoroughly investigate its antifibrotic mechanism of action.…”

Section: Discussionmentioning

confidence: 98%

Dapagliflozin alleviates cardiac fibrosis through suppressing EndMT and fibroblast activation via AMPKα/TGF‐β/Smad signalling in type 2 diabetic rats

Tian

Zhang

Suo

et al. 2021

J Cellular Molecular Medi

105

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Diabetic cardiomyopathy (DCM) is one of the leading causes of heart failure in patients with diabetes mellitus, with limited effective treatments. The cardioprotective effects of sodium‐glucose cotransporter 2(SGLT2) inhibitors have been supported by amounts of clinical trials, which largely fills the gap. However, the underlying mechanism still needs to be further explored, especially in terms of its protection against cardiac fibrosis, a crucial pathophysiological process during the development of DCM. Besides, endothelial‐to‐mesenchymal transition (EndMT) has been reported to play a pivotal role in fibroblast multiplication and cardiac fibrosis. This study aimed to evaluate the effect of SGLT2 inhibitor dapagliflozin (DAPA) on DCM especially for cardiac fibrosis and explore the underlying mechanism. In vivo, the model of type 2 diabetic rats was built with high‐fat feeding and streptozotocin injection. Untreated diabetic rats showed cardiac dysfunction, increased myocardial fibrosis and EndMT, which was attenuated after treatment with DAPA and metformin. In vitro, HUVECs and primary cardiac fibroblasts were treated with DAPA and exposed to high glucose (HG). HG‐induced EndMT in HUVECs and collagen secretion of fibroblasts were markedly inhibited by DAPA. Up‐regulation of TGF‐β/Smad signalling and activity inhibition of AMPKα were also reversed by DAPA treatment. Then, AMPKα siRNA and compound C abrogated the anti‐EndMT effects of DAPA in HUVECs. From above all, our study implied that DAPA can protect against DCM and myocardial fibrosis through suppressing fibroblast activation and EndMT via AMPKα‐mediated inhibition of TGF‐β/Smad signalling.

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“…Curcumenol has a variety of pharmacological and biological activities, including antitumor activity, treatment of nerve and mental diseases, and antiliver fibrosis [ 42 – 44 ]. Studies confirmed that curcumenol has antitumor effects on gastric cancer, colorectal cancer, and breast cancer [ 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Curcumenol Targeting YWHAG Inhibits the Pentose Phosphate Pathway and Enhances Antitumor Effects of Cisplatin

Mao

Zhong

Zhuang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Cervical cancer is a common cancer in women. The drug resistance of chemotherapeutic agents has always been an urgent problem to be solved in clinics. The purpose of this study was to determine the role of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma polypeptide (YWHAG) in cervical cancer and explore the effect of Curcuma on cervical cancer and its possible mechanism. Methods. YWHAG expression in cervical cancer was confirmed using The Cancer Genome Atlas (TCGA) database. Then, the effects of YWHAG on the proliferation and invasion of HeLa and C33A cervical cancer cells were detected by the cell counting kit-8 (CCK-8) and transwell assay. The relationship between YWHAG and the pentose phosphorylation pathway was further studied. CCK-8, Edu, and quantitative real-time polymerase chain reaction were used to confirm that Curcuma inhibited the sensitivity of YWHAG to cisplatin chemotherapy and to detect the expression of apoptosis-related proteins. Results. YWHAG was highly expressed in cervical cancer and was associated with poor prognosis. The proliferation and invasion abilities of HeLa and C33A cells decreased after YWHAG knockout. The TCGA database of cervical cancer showed a positive correlation between YWHAG and hypoxia-inducible factor-1 subunit alpha (HIF-1α) expression. YWHAG expression increased with HIF-1α overexpression. YWHAG knockdown reduced the protein expression in the pentose phosphorylation pathway. Curcumenol inhibited YWHAG expression. Compared with cisplatin alone, curcumenol combined with cisplatin can reduce cell proliferation and invasion and reduce matrix metalloproteinase (MMP) 2 and MMP9 expression. It can also increase apoptosis, decrease B cell lymphoma 2 (Bcl-2) expression, and increase the expression of Bcl-2 antagonist X, caspase-3, and polyadenosine diphosphate-ribose polymerase. Conclusion. YWHAG can interact with HIF-1α to affect the proliferation and invasion of cervical cancer cells. YWHAG knockout can reduce the expression of pentose phosphorylation pathway-related proteins. Curcumenol can enhance cisplatin to inhibit cancer cell proliferation, migration, and invasion and promote tumor cell apoptosis. The combination of drugs may promote the apoptosis of cervical cancer cells through the YWHAG pathway.

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Curcumol enhances the anti-tumor effects of metformin via suppressing epithelial-mesenchymal transition in triple-negative breast cancer

Cited by 16 publications

References 49 publications

Curcumol increases the sensitivity of colon cancer to 5-FU by regulating Wnt/β-catenin signaling

Curcumol increases the sensitivity of colon cancer to 5-FU by regulating Wnt/β-catenin signaling

Dapagliflozin alleviates cardiac fibrosis through suppressing EndMT and fibroblast activation via AMPKα/TGF‐β/Smad signalling in type 2 diabetic rats

Curcumenol Targeting YWHAG Inhibits the Pentose Phosphate Pathway and Enhances Antitumor Effects of Cisplatin

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