Synergistic Effect of Combined Treatment with Longan Flower Extract and 5-Fluorouracil on Colorectal Cancer Cells

Chen, Szu-Jung; Chung, Yuan‐Chiang; Chang, Han-Lung; Chang, Hsin-Ping; Chou, Jui-ling; Lin, Chih‐Cheng; Chen, Chih-Hsien; Hsu, Chih‐Ping

doi:10.1080/01635581.2019.1622739

Cited by 12 publications

(6 citation statements)

References 21 publications

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“…It is established that 5-FU exerts its cytotoxic effects in tumor cells primarily through inhibition of DNA synthesis. This is evident in the significant arrests of G 1 /S and S phases of cell cycle, as well as reduced G 2 /M phase population in colon cancer cells post-5-FU treatment [ 28 , 64 ]. 5-FU-resistant cells typically exhibit attenuated effects of 5-FU cytotoxicity with a higher population of cells detected in both G 1 /S and S phases when compared to 5-FU-susceptible cells [ 27 , 28 , 65 , 66 ].…”

Section: Classical Mechanisms Of Resistancementioning

confidence: 99%

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Azwar

Seow

Abdullah

et al. 2021

Biology

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5-Fluorouracil (5-FU) plus leucovorin (LV) remain as the mainstay standard adjuvant chemotherapy treatment for early stage colon cancer, and the preferred first-line option for metastatic colon cancer patients in combination with oxaliplatin in FOLFOX, or irinotecan in FOLFIRI regimens. Despite treatment success to a certain extent, the incidence of chemotherapy failure attributed to chemotherapy resistance is still reported in many patients. This resistance, which can be defined by tumor tolerance against chemotherapy, either intrinsic or acquired, is primarily driven by the dysregulation of various components in distinct pathways. In recent years, it has been established that the incidence of 5-FU resistance, akin to multidrug resistance, can be attributed to the alterations in drug transport, evasion of apoptosis, changes in the cell cycle and DNA-damage repair machinery, regulation of autophagy, epithelial-to-mesenchymal transition, cancer stem cell involvement, tumor microenvironment interactions, miRNA dysregulations, epigenetic alterations, as well as redox imbalances. Certain resistance mechanisms that are 5-FU-specific have also been ascertained to include the upregulation of thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, and the downregulation of thymidine phosphorylase. Indeed, the successful modulation of these mechanisms have been the game plan of numerous studies that had employed small molecule inhibitors, plant-based small molecules, and non-coding RNA regulators to effectively reverse 5-FU resistance in colon cancer cells. It is hoped that these studies would provide fundamental knowledge to further our understanding prior developing novel drugs in the near future that would synergistically work with 5-FU to potentiate its antitumor effects and improve the patient’s overall survival.

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Section: Classical Mechanisms Of Resistancementioning

confidence: 99%

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Azwar

Seow

Abdullah

et al. 2021

Biology

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“…Piper betle was found to enhance the anticancer activity of 5-FU in HT-29 and HCT116 colon cancer cells [ 22 ]. A longan flower extract was found to produce synergistic anticancer effects in CRC cells when used in combination with 5-FU through mitochondria-dependent apoptosis [ 23 ]. Rutin, a glycoside found in green tea and apple trees, exhibited synergistic drug-herb interactions in combination with 5-FU, to induce apoptosis in prostate cancer cells [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Calotropis gigantea stem bark extract induced apoptosis related to ROS and ATP production in colon cancer cells

et al. 2021

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Conventional chemotherapeutic agents for colorectal cancer (CRC) cause systemic side effects and eventually become less efficacious owing to the development of drug resistance in cancer cells. Therefore, new therapeutic regimens have focused on the use of natural products. The anticancer activity of several parts of Calotropis gigantea has been reported; however, the effects of its stem bark extract on inhibition of cancer cell proliferation have not yet been examined. In this study, the anticancer activity of C. gigantea stem bark extract, both alone and in combination with 5-fluorouracil (5-FU), was evaluated. A crude ethanolic extract was prepared from dry, powdered C. gigantea barks using 95% ethanol. This was then partitioned to obtain dichloromethane (CGDCM), ethyl acetate, and water fractions. Quantitative analysis of the constituent secondary metabolites and calotropin was performed. These fractions exhibited cytotoxicity in HCT116 and HT-29 cells, with CGDCM showing the highest potency in both the cell lines. A combination of CGDCM and 5-FU significantly enhanced the cytotoxic effect. Moreover, the resistance of normal fibroblast, HFF-1, cells to this combination demonstrated its safety in normal cells. The combination significantly enhanced apoptosis through the mitochondria-dependent pathway. Additionally, the combination reduced adenosine triphosphate production and increased the production of reactive oxygen species, demonstrating the mechanisms involved in the induction of apoptosis. Our results suggest that CGDCM is a promising anti-cancer agent and may enhance apoptosis induction by 5-FU in the treatment of CRC, while minimizing toxicity toward healthy cells.

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“…Combined therapy has shown a variety of advantages over monotherapy, including decreasing the concentration and toxicity of drugs, improving efficiency, targeting multiple molecular pathways, and sensitizing cells to treatment [ 68 ]. As the above statements make clear, the definition of synergy can overlap with potentiation.…”

Section: Resultsmentioning

confidence: 99%

Anti-Inflammatory, Antioxidant Activities, and Phytochemical Characterization of Edible Plants Exerting Synergistic Effects in Human Gastric Epithelial Cells

et al. 2023

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Dietary bioactive compounds from natural sources (e.g., herbal medicines, foods) are known to potentially suppress acute or chronic inflammation and promote the effectiveness of treatment to reduce the harmful effects of gastritis alone or in combination. In this regard, we have characterized four Cameroonian spice extracts, namely Aframomum citratum, Dichrostachys glomerata, Tetrapleura tetraptera, and Xylopia parviflora through reverse phase-high-performance liquid chromatography (RP-HPLC), ultra-performance liquid chromatography-electrospray ionization high-resolution mass spectrometry (UPLC-ESI-HRMS/MS), and Fourier transform infrared spectroscopic (FTIR) analyses and investigated their antioxidant and synergistic anti-inflammatory activities in human gastric adenocarcinoma (AGS) and gastric epithelial (GES-1) cells. The extracts showed a high amount of total phenolic (TPC: 150–290 mg gallic acid equivalents (GAE)/g of extract) and flavonoid content (TFC: 35–115 mg catechin equivalents (CE)/g of extract) with antioxidant properties in a cell-free system (1,1-Diphenyl-2-picryl-hydrazyl (DPPH) half maximal inhibitory concentration (IC50s) ≤ 45 µg/mL; 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) half maximal inhibitory concentration (IC50s) ≤ 29 µg/mL. The extracts in combination (MIX) exert a synergistic beneficial effect (combination index (CIs) < 1 and dose reduction index (DRIs) > 1) on inflammatory markers (interleukin (IL)-8 and -6 release, and nuclear factor kappa B (NF-κB) driven transcription) in human gastric epithelial cells, which may result from the presence of phenolic compounds (phenolic acids, flavonoids) or other compounds (protein, lipid, aromatic, and polysaccharide compounds) tentatively identified in the extracts. The general findings of the present study provide supporting evidence on the chemical composition of four Cameroonian dietary plants and their significant synergistic inhibitory activities on inflammatory markers of gastric epithelial cells.

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Synergistic Effect of Combined Treatment with Longan Flower Extract and 5-Fluorouracil on Colorectal Cancer Cells

Cited by 12 publications

References 21 publications

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Calotropis gigantea stem bark extract induced apoptosis related to ROS and ATP production in colon cancer cells

Anti-Inflammatory, Antioxidant Activities, and Phytochemical Characterization of Edible Plants Exerting Synergistic Effects in Human Gastric Epithelial Cells

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