Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells

Li, Guoli; Fang, Sining; Shao, Xueming; Li, Yejia; Tong, Qingchao; Kong, Beibei; Chen, Lifen; Wang, Yanzhong; Yang, Jun; Yu, Haitao; Xie, Xinyou; Zhang, Jun

doi:10.3390/biom11091295

Cited by 43 publications

(35 citation statements)

References 42 publications

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“…ROS are cellular signaling proteins that are involved in every phase of cellular metabolism (Ye et al., 2021b ). Cur can increase the production of ROS, leading to many dysfunctions in cells, including DNA damage, apoptosis, and cell cycle arrest in cancer cells (Li et al., 2021 ). To verify the mechanism of inducing apoptosis, ROS production in cancer cells was detected by a ROS probe.…”

Section: Resultsmentioning

confidence: 99%

Selective delivery of curcumin to breast cancer cells by self-targeting apoferritin nanocages with pH-responsive and low toxicity

Wang

Yin

et al. 2022

Drug Delivery

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Breast cancer is prevalent and diverse with significantly high incidence and mortality rates. Curcumin (Cur), a polyphenol component of turmeric, has been widely recognized as having strong anti-breast cancer activity. However, its anti-cancer efficiency is largely impaired by some of its concomitant negative properties, including its poor solubility, low cellular uptake, and severe reported side effects. Hence, the necessity arises to develop a novel low-toxic and high-efficiency targeting drug delivery system (DDS). In this study, we developed a pH-sensitive tumor self-targeting DDS (Cur@HFn) based on self-assembled HFn loaded with Cur, in which Cur was encapsulated into HFn cavity by using a disassembly/reassembly strategy, and the Cur@HFn was characterized by ultraviolet–visible (UV–vis), dynamic light scattering (DLS), and transmission electron microscope (TEM). A variety of breast cancer cell models were built to evaluate cytotoxicity, apoptosis, targeting properties, and uptake mechanism of the Cur@HFn. The pharmacodynamics was also evaluated in tumor (4T1) bearing mice after intravenous injection. In vitro release experiments showed that Cur@HFn is pH sensitive and shows sustained drug release under slightly acidic conditions. Compared with Cur, Cur@HFn has stronger cytotoxicity, cellular uptake, and targeting performance. Our study supported that Cur@HFn has a higher in vivo therapeutic effect and lower systemic toxicity. The safety evaluation results indicated that Cur@HFn has no hematotoxicity, hepatotoxicity, and nephrotoxicity. The findings of the present study showed that the Cur@HFn has been successfully prepared and has potential application value in the treatment of breast cancer.

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Section: Resultsmentioning

confidence: 99%

Selective delivery of curcumin to breast cancer cells by self-targeting apoferritin nanocages with pH-responsive and low toxicity

Wang

Yin

et al. 2022

Drug Delivery

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“…Results showed that the m 6 A demethylase FTO was positively associated Overall survival with CPEB1 in both colon and stomach adenocarcinoma (Figure 5A). Knockdown of FTO significantly decreased the expression of CPEB1 (Figure 5B), which suggested that m 6 A modification could be involved in the increase levels of CPEB1 in colon and stomach adenocarcinoma cells. In subsequent study, a RIP assay validated m 6 A modification of CPEB1 mRNA in colon and stomach adenocarcinoma cells and also confirmed the role played by FTO in this modification (Figure 5C).…”

Section: Fto-induced M 6 a Modification Is Responsible For Increasing...mentioning

confidence: 88%

“…Knockdown of FTO significantly decreased the expression of CPEB1 (Figure 5B), which suggested that m 6 A modification could be involved in the increase levels of CPEB1 in colon and stomach adenocarcinoma cells. In subsequent study, a RIP assay validated m 6 A modification of CPEB1 mRNA in colon and stomach adenocarcinoma cells and also confirmed the role played by FTO in this modification (Figure 5C). As shown in Figure 5D, the expression levels of FTO and CPEB1 were increased in tumor tissues compared to their adjacent normal tissues (Figure 5D,5E).…”

Section: Fto-induced M 6 a Modification Is Responsible For Increasing...mentioning

confidence: 88%

“…Nine patients with colorectal adenocarcinoma and six patients with gastric adenocarcinoma who were treated at Changhai Hospital were enrolled in this study. Tumor and adjacent normal tissues from these patients were subjected to quantitative real-time PCR (qRT-PCR) and m 6 A methylated RNA immunoprecipitation quantitative PCR (meRIP qPCR). The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).…”

Section: Patients and Treatmentmentioning

confidence: 99%

“…Since its discovery in 1957, 5-fluorouracil (5-FU) has been used as a first-line treatment for colorectal cancer (CRC) (1)(2)(3)(4). Nevertheless, the efficacy of 5-FU-based chemotherapy for CRC is disappointing, as most patients acquire drug resistance during treatment, resulting in a median survival time of only about 20 months (5,6). Furthermore, for patients with gastric cancer (GC), the benefits of palliative chemotherapy and supportive treatment are limited, with a response rate ranging from 25% to 50% and the median survival being 6 to 12 months (7).…”

Section: Introductionmentioning

confidence: 99%

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Low CPEB1 levels may predict the benefit of 5-fluorouracil treatment in patients with colon or stomach adenocarcinoma

Cao¹,

Niu²,

Huang³

et al. 2022

J Gastrointest Oncol

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Background: For patients with colon or stomach adenocarcinoma, 5-fluorouracil (5-FU) is an essential component of systemic chemotherapy in the palliative and adjuvant settings. The post-transcriptional regulatory factor cytoplasmic polyadenylation element-binding protein 1 (CPEB1) has been reported to be linked to tumor metastasis. This study aimed to investigate the relationship between CPEB1 expression and 5-FU treatment response in patients with colon and stomach adenocarcinomas. Methods:The expression of CPEB1 in stomach adenocarcinoma and colorectal cancer (CRC) tissues and in cell lines was determined by quantitative real-time PCR (qRT-PCR) and immunohistochemistry analyses.Transwell assays were employed to analyze the effects of CPEB1 on the migration and invasion abilities of gastric cancer (GC) and CRC cells. Results:The expression levels of CPEB1 were increased in colon and stomach adenocarcinoma and were negatively correlated with malignancy and poor patient survival. Data suggested that patients with CRC or GC who had strong CPEB1 expression responded poorly to 5-FU treatment. Furthermore, knockdown of CPEB1 inhibited the migration and invasion of CRC and GC cells via a mechanism involving decreased expression of matrix metalloprotein (MMP)2, 7, and 9. Finally, our methylated RNA immunoprecipitation PCR (meRIP qPCR) data suggested that the increased CPEB1 expression in colon and stomach adenocarcinomas might be mediated by FTO (FTO alpha-ketoglutarate dependent dioxygenase)-dependent m 6 A demethylation of CPEB1 mRNA. Conclusions:Our results indicate that the level of CPEB1 expression may be valuable for predicting the benefit of 5-FU treatment for patients with colon and stomach adenocarcinomas. We therefore propose that low CPEB1 expression may represent a novel biomarker for personalized 5-FU therapy.

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Sclareol induces cell cycle arrest and ROS‐mediated apoptosis and ferroptosis in lung adenocarcinoma cells

Rah,

Shafarin,

Hamad

et al. 2023

J Biochem & Molecular Tox

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Sclareol (SC) has shown significant anticancer activity against breast and colon cancers among others. However, its ability to precipitate similar anticancer effects in lung cancer has yet to be investigated. To address this issue, SC‐treated lung adenocarcinoma cells (A549) were assessed for viability and functional competence as well as the expression of genes related to apoptosis and cell cycling. Our results demonstrated that SC treatment inhibited A549 cell clonogenic features and reduced their migration and invasion potential in a dose‐dependent manner. Mechanistically, SC treatment downregulated the expression of cyclin D1 and survivin and upregulated that of p21 and p16, which was associated with a significant increase in the percentage of SubG0 cells. SC treatment is also associated with the induction of both the extrinsic and intrinsic apoptotic pathways, as evidenced by the increased expression and splitting of PARP1 and procaspases 3 and 9 and the reduced expression of antiapoptotic proteins Bcl‐2 and Bcl‐xL. Increased cell death in SC‐treated cells is likely to have resulted from the induction of ferroptosis as suggested by the reduced expression of FPN and the inhibition of the anti‐ferroptosis regulator GPX4. In conclusion, the data presented here suggest that SC can reduce lung carcinoma cell growth and metastasis and promote cell death.

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Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells

Cited by 43 publications

References 42 publications

Selective delivery of curcumin to breast cancer cells by self-targeting apoferritin nanocages with pH-responsive and low toxicity

Selective delivery of curcumin to breast cancer cells by self-targeting apoferritin nanocages with pH-responsive and low toxicity

Low CPEB1 levels may predict the benefit of 5-fluorouracil treatment in patients with colon or stomach adenocarcinoma

Sclareol induces cell cycle arrest and ROS‐mediated apoptosis and ferroptosis in lung adenocarcinoma cells

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