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Published on: December 2, 2022
Inhibitory effects of four plants flavonoids extracts on fatty acid synthase
Jun Chen1, Donghong Zhuang2, Weijia Cai3
1Department of Biology, Shantou University, Shantou 515063, China; Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, China.
Abstract:
Fatty acid synthase (FAS) had been found overexpress and hyperactive in most cancers. Pharmacological inhibitors of FAS activity preferentially repress cancer cell proliferation and induce cancer cell apoptosis without affecting nonmalignant fibroblasts. These made FAS an excellent drug target for cancer therapy. The activity of FAS in 11 different kinds of cancer cells, including esophageal carcinoma (EC109, EC8712, H5E973), gastric carcinoma (N87, BGC823), lung carcinoma (A549, 95-D), hepatoma (HepG2), uterine cervix cancer (HeLa) and leukaemia (K562, U937) were compared using spectrophotometric method. We selected the cell line with the highest FAS activity as cell model to study the inhibitory effect of the flavonoids extracts on FAS. Four plants including Canavium album Raeuseh leaves, Bombax ceiba Linn, Brassica albograbra Bailey, and Citrus reticulata Blanco were selected for extracting flavonoids. The results showed significantly different FAS activity among different cancer cells. The FAS activity is the lowest in gastric cancer cell N87 (15.91 ± 3.61 U/mg protein) and the highest in lung cancer cell A549 (127.36 ± 10.14 U/mg protein). The cancer cell A549 was used as cell model to test the inhibitory effort of flavonoids extracts on FAS. Results showed that the flavonoids extracts of Citrus reticulata Blanco and Canavium album Raeuseh leaves have higher inhibitory effect on FAS activity compared with the universally used FAS inhibitor C75 and both extracts inhibit cancer cell proliferation when added to cultured cancer cells. These studies provided a good cell model for testing the inhibitory effect on FAS activity and suggested that Citrus reticulata Blanco rind and Canavium album Raeuseh leaves are good biomaterials for separating and purifying natural flavonoids FAS inhibitors and exploring their inhibitory mechanisms.
Insights
Fatty acid synthase (FAS) is overactive in many cancers, making it a drug target. Citrus reticulata Blanco and Canavium album Raeuseh leaf flavonoids show potent FAS inhibition, offering natural cancer therapy potential.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Fatty acid synthase (FAS) is frequently overexpressed and hyperactive in various cancers.
- FAS hyperactivity drives cancer cell proliferation and survival, making it a promising therapeutic target.
- Inhibiting FAS preferentially affects cancer cells over normal cells, highlighting its specificity.
Purpose of the Study:
- To compare FAS activity across 11 human cancer cell lines.
- To establish a cell model with high FAS activity for evaluating natural inhibitors.
- To investigate the inhibitory effects of flavonoid extracts from selected plants on FAS activity.
Main Methods:
- Spectrophotometric assays were used to quantify FAS activity in esophageal, gastric, lung, hepatoma, cervical, and leukemia cancer cell lines.
- The A549 lung cancer cell line, exhibiting the highest FAS activity, was selected as the experimental model.
- Flavonoid extracts from Canavium album Raeuseh leaves, Bombax ceiba Linn, Brassica albograbra Bailey, and Citrus reticulata Blanco were prepared and tested for FAS inhibition.
Main Results:
- Significant variations in FAS activity were observed among the tested cancer cell lines, with A549 showing the highest activity (127.36 ± 10.14 U/mg protein).
- Flavonoid extracts from Citrus reticulata Blanco and Canavium album Raeuseh leaves demonstrated superior FAS inhibitory effects compared to the standard inhibitor C75.
- Both effective flavonoid extracts inhibited the proliferation of cultured cancer cells.
Conclusions:
- The A549 cell line serves as an effective model for studying FAS inhibitors.
- Citrus reticulata Blanco rind and Canavium album Raeuseh leaves are valuable sources for natural FAS inhibitors.
- These findings support the development of natural flavonoids as potential therapeutic agents for cancer treatment.
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