Hoạt động chống oxy hóa hoặc tạo oxy hóa và khả năng ức chế glutathione transferase P1-1 của hạt Tamarindus indica và tác động gây độc tế bào của nó lên dòng tế bào ung thư MCF-7

R. A. Guneidy1, A. M. Gad1, E. R. Zaki1, F. M. Ibrahim2, A. Shokeer1
1Molecular Biology Department, National Research Centre, Cairo, Egypt
2Medicinal and Aromatic Plants Research Department, National Research Centre, Cairo, Egypt

Tóm tắt

Kháng thuốc đa (MDR) của các tế bào ung thư là một trở ngại lớn trong điều trị ung thư. Glutathione S-transferase Pi (GSTP1-1) xúc tác phản ứng liên hợp của glutathione với các loại thuốc chống ung thư, từ đó làm giảm hiệu quả của chúng. Các hợp chất phenolic có khả năng ức chế hoạt động của GSTP1-1, đây là một mục tiêu đầy hứa hẹn để vượt qua MDR và tăng cường hiệu quả hóa trị. Ba phân đoạn (dichloromethane, ethyl acetate và n-butanol) đã được chuẩn bị từ hạt cây me để xác định các tính chất phenolic và flavonoid cũng như các thuộc tính chống oxy hóa/tạo oxy hóa của chúng. Phân đoạn n-butanol thể hiện mức phenol cao nhất (378 ± 11.7 mg tương đương axit gallic/g khối lượng khô) và flavonoid (83 ± 6.0 mg tương đương rutin/g khối lượng khô). Các tác động ức chế lên hoạt động GSTP1-1 tinh khiết trong hồng cầu người (eGST), nhau thai (pGST) và hGSTP1-1 đã được nghiên cứu. Phân đoạn n-butanol là hiệu quả nhất trong việc ức chế eGST, hGSTP1-1 và pGST với các giá trị IC50 lần lượt là 3.0 ± 0.7, 4.85 ± 0.35 và 6.6 ± 1.2 μg/ml. Độc tính tế bào đã được nghiên cứu với phân đoạn n-butanol của T. indica trên nhiều dòng tế bào ung thư người khác nhau. Duy nhất hai dòng tế bào bị ảnh hưởng là MCF-7 (72%) và HePG2 (52%) cho thấy độc tính tế bào. Giá trị IC50 của phân đoạn n-butanol T. indica được quan sát là 68.5 μg/ml so với 1.7 μg/ml tamoxifen trong dòng tế bào MCF-7. Sự kết hợp điều trị giữa chiết xuất T. indica với thuốc đã được phê duyệt về mặt y học là tamoxifen có những tác động bất ngờ; sự loại bỏ hoàn toàn hiệu ứng ức chế gây độc tế bào của tamoxifen và chiết xuất thực vật được quan sát. Tuy nhiên, chiết xuất T. indica có tác động gây độc tế bào đối với dòng tế bào MCF-7; trong một số tình huống, các sản phẩm thực vật có thể có tác động ngược lại so với loại thuốc dự định, từ đó làm giảm tác động của thuốc.

Từ khóa

#kháng thuốc đa #glutathione S-transferase Pi #hợp chất phenolic #ức chế hoạt động #độc tính tế bào #dòng tế bào ung thư MCF-7 #chiết xuất thực vật #tamoxifen

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