Sex-Dependent Adverse Drug Reactions to 5-Fluorouracil in Colorectal Cancer

Lim, Hyesol; Kim, Sun Young; Lee, Eun‐Hye; Lee, Seung‐Eun; Oh, Sungryong; Jung, Joohee; Kim, Kwi Suk; Moon, Aree

doi:10.1248/bpb.b18-00707

Cited by 19 publications

(15 citation statements)

References 27 publications

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“…The most sensitive cell line was SK-MES-1, with a value of 8.625 μM, followed by BJ cells, with a value of 33.17 μM, and the least sensitive cell line was DLD-1, with a value of 53.53 μM, showing different effects compared to 5-FU alone. , and lung squamous adenocarcinoma (SK-MES-1) cells, with similar IC50, when incubated for 24 h (6,12,24,48,96,192, and 385 μM 5-FU). The results with p < 0.05 were considered statistically significant (* p < 0.05, ** p < 0.01, and *** p < 0.001).…”

Section: The Effect Of 5-fu and Allicin Alone And In Combination On Tmentioning

confidence: 92%

“…The viability rate analysis of 5-fluorouracil (5-FU) treatment. 5-FU inhibited cell growth in a dose-dependent manner in the case of normal fibroblasts (BJ), colorectal adenocarcinoma (DLD-1), and lung squamous adenocarcinoma (SK-MES-1) cells, with similar IC 50 , when incubated for 24 h (6,12,24,48,96,192, and 385 µM 5-FU). The results with p < 0.05 were considered statistically significant (* p < 0.05, ** p < 0.01, and *** p < 0.001).…”

Section: Figurementioning

confidence: 97%

“…Both lung and colorectal cancers are estimated to be responsible for more than 2.5 million deaths worldwide [3]. Different synthesized chemical compounds are used for cancer therapy [4], and 5-fluorouracil (5-FU) is one of the most commonly used first-line anticancer drugs in clinical practice [5,6]. 5-FU is commonly prescribed for solid tumor types [7] and is widely used as an essential chemotherapeutic agent for colorectal cancer [6], gastric cancer [5], and hepatocellular carcinoma [8].…”

Section: Introductionmentioning

confidence: 99%

“…Different synthesized chemical compounds are used for cancer therapy [4], and 5-fluorouracil (5-FU) is one of the most commonly used first-line anticancer drugs in clinical practice [5,6]. 5-FU is commonly prescribed for solid tumor types [7] and is widely used as an essential chemotherapeutic agent for colorectal cancer [6], gastric cancer [5], and hepatocellular carcinoma [8]. Moreover, 5-FU is most often used in combination with other specific cancer drugs to treat many types of cancer, including breast cancer, head and neck cancers, anal cancer, stomach cancer, colon cancer, and some skin cancers [9].…”

Section: Introductionmentioning

confidence: 99%

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The Synergistic Antitumor Effect of 5-Fluorouracil Combined with Allicin against Lung and Colorectal Carcinoma Cells

et al. 2020

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5-fluorouracil (5-FU) is an anticancer drug used to inhibit the proliferation of many different tumor cells. Since severe events are associated with this compound, its combination with different anticancer drugs or adjuvants would allow the use of a significantly lower dose of 5-FU. In this study, we highlighted that the combination of allicin with 5-FU inhibited the cell migration and proliferation of colorectal and lung cancer cells. 5-FU inhibited cell growth with a similar inhibitory concentration for both normal and tumor cells (~200µM), while allicin showed different inhibitory concentrations. With an IC50 of 8.625 µM, lung cancer cells were the most sensitive to allicin. Compared to 5-FU and allicin single-agent treatments, the co-treatment showed a reduced viability rate, with p < 0.05. The morphological changes were visible on all three cell lines, indicating that the treatment inhibited the proliferation of both normal and tumor cells. We highlighted different cell death mechanisms—apoptosis for lung cancer and a non-apoptotic cell death for colorectal cancer. The synergistic antitumor effect of 5-FU combined with allicin was visible against lung and colorectal carcinoma cells. Better results were obtained when a lower concentration of 5-FU was combined with allicin than the single-agent treatment at IC50.

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Section: The Effect Of 5-fu and Allicin Alone And In Combination On Tmentioning

confidence: 92%

Section: Figurementioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Synergistic Antitumor Effect of 5-Fluorouracil Combined with Allicin against Lung and Colorectal Carcinoma Cells

et al. 2020

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“…Among these, chemotherapy is the most common strategy (Wang et al, 2014b;Pohl and Schmiegel, 2016). However, the two major challenges for the effective treatment of colon cancer are adverse effects due to cancer chemotherapy and drug resistance (Kozovska et al, 2014;Lim et al, 2019). Hence, it is imperative to search for new chemotherapeutic agents that have better safety and efficacy profiles.…”

Section: Introductionmentioning

confidence: 99%

Hydroxypropyl-β-Cyclodextrin Complexes of Styryllactones Enhance the Anti-Tumor Effect in SW1116 Cell Line

Chen

et al. 2020

Front. Pharmacol.

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Styryllactones, a class of compounds obtained from the genus Goniothalamus (Annonaceae), have demonstrated in vitro antitumor activity. However, the aqueous solubility of these compounds is poor. In this study, we identified the absolute configurations of the previously isolated compounds, which were first isolated in our laboratory, by single-crystal X-ray diffraction analysis using Cu Ka radiation. Subsequently, the antitumor activities of the compounds were evaluated by 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide staining in four tumor cell lines. The induced apoptosis activity of leiocarpin E-7ʹ-Monoacetate was studied by an annexin V fluorescein isothiocyanate/propidium iodide double-staining experiment, and the caspase activity was tested in the SW1116 cell line. The results demonstrated that the antitumor activities of cheliensisin A and goniodiol-7-monoacetate were limited by their poor water solubility. To address this issue, hydroxypropyl-b-cyclodextrin (HP-b-CD) complexes of the compounds were synthesized by the saturated aqueous method. The complexes were then analyzed using a differential scanning calorimeter. The IC 50 of cheliensisin A was reduced by 45% and 58% against SW1116 and SMMC-7721 cell lines, respectively. Similarly, the IC 50 of goniodiol-7-monoacetate was reduced by 55% and 34% against the two tumor cell lines, respectively. To further evaluate whether the styryllactones and complexes possessed selectivity against cancer cell lines and normal cell lines, toxicity against human normal cell line (HEK293T) was evaluated. The results demonstrated that the HP-b-CD complexes displayed more cytotoxicity than the respective pristine compounds against the HEK293T cell line. However, there existed a therapeutic window when the complexes were applied against cancer cell lines. In summary, the synthesis of several styryllactone compounds complexed with HP-b-CD was reported for the first time. These complexes could significantly enhance the cytotoxic effects of styryllactone compounds.

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Individualized Dosing of Fluoropyrimidine‐Based Chemotherapy to Prevent Severe Fluoropyrimidine‐Related Toxicity: What Are the Options?

Knikman

Gelderblom

Beijnen

et al. 2020

Clin Pharma and Therapeutics

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Fluoropyrimidines are widely used in the treatment of several types of solid tumors. Although most often well tolerated, severe toxicity is encountered in ~ 20–30% of the patients. Individualized dosing for these patients can reduce the incidence of severe fluoropyrimidine‐related toxicity. However, no consensus has been achieved on which dosing strategy is preferred. The most established strategy for individualized dosing of fluoropyrimidines is upfront genotyping of the DPYD gene. Prospective research has shown that DPYD‐guided dose‐individualization significantly reduces the incidence of severe toxicity and can be easily applied in routine daily practice. Furthermore, the measurement of the dihydropyrimidine dehydrogenase (DPD) enzyme activity has shown to accurately detect patients with a DPD deficiency. Yet, because this assay is time‐consuming and expensive, it is not widely implemented in routine clinical care. Other methods include the measurement of pretreatment endogenous serum uracil concentrations, the uracil/dihydrouracil‐ratio, and the 5‐fluorouracil (5‐FU) degradation rate. These methods have shown mixed results. Next to these methods to detect DPD deficiency, pharmacokinetically guided follow‐up of 5‐FU could potentially be used as an addition to dosing strategies to further improve the safety of fluoropyrimidines. Furthermore, baseline characteristics, such as sex, age, body composition, and renal function have shown to have a relationship with the development of severe toxicity. Therefore, these baseline characteristics should be considered as a dose‐individualization strategy. We present an overview of the current dose‐individualization strategies and provide perspectives for a future multiparametric approach.

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Sex-Dependent Adverse Drug Reactions to 5-Fluorouracil in Colorectal Cancer

Cited by 19 publications

References 27 publications

The Synergistic Antitumor Effect of 5-Fluorouracil Combined with Allicin against Lung and Colorectal Carcinoma Cells

The Synergistic Antitumor Effect of 5-Fluorouracil Combined with Allicin against Lung and Colorectal Carcinoma Cells

Hydroxypropyl-β-Cyclodextrin Complexes of Styryllactones Enhance the Anti-Tumor Effect in SW1116 Cell Line

Individualized Dosing of Fluoropyrimidine‐Based Chemotherapy to Prevent Severe Fluoropyrimidine‐Related Toxicity: What Are the Options?

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