Toumi Iheb, Yatouji Sonia, Borie Nicolas, Remy Simon, Renault Jean-Hugues, Chazee Lise, Hammami Mohamed, Martiny Laurent, Devarenne-Charpentier Emmanuelle, El Btaouri Hassan
Laboratoire de Biochimie, LR12ES05, Faculté de Médecine, Université de Monastir, 5019 Monastir, Tunisie.
UMR-CNRS 7312 Institut de Chimie Moléculaire de Reims (ICMR), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, BP 1039, 51687 Reims cedex, FRANCE.
Anticancer Agents Med Chem. 2023;23(6):687-698. doi: 10.2174/1871520622666220826095035.
Conventional chemotherapeutic treatment of colorectal cancer has low efficiency because of its high toxicity. Several studies identified natural compounds as potential antitumor agents by inducing cancer cell cycle arrest or apoptosis and exhibiting a potential synergy in drug combination therapy. Natural compounds derived from plants represent an important source of pharmacologic agents toward several diseases. For example, the Tunisian Thymelaeaceae plants are used in folk medicine for the treatment of different pathologies such as diabetes and hypertension.
The Thymelaea hirsuta L. extracts were evaluated for their anti-tumoral activities and their adjuvant potential that could be used in conventional colorectal cancer therapy.
Fractionation of total methanolic extract from the plant leaves provided 4 fractions using vacuum liquid chromatography. The cytotoxic activities of these fractions were tested toward colorectal cancer cells.
Ethyl acetate fraction (E2 fraction) induced cell cycle arrest and apoptosis by activating caspase-3. E2 fraction inhibited cell invasion by reducing integrin α5 expression and FAK phosphorylation. Moreover, E2 fraction potentialized colorectal cancer cells to 5-FU treatment.
The selected plant Thymelaea hirsuta is the source of natural compounds that inhibited cell growth and invasion and induced cell cycle arrest in colorectal cancer cells. The most interesting result was their potential synergy in 5-FU combination treatment. Further analysis will identify the active compounds and confirm their role in chemotherapeutic treatment by sensitizing colorectal cancer cell to anti-cancer drugs.
由于毒性高，传统的结直肠癌化疗治疗效率低下。多项研究通过诱导癌细胞周期停滞或凋亡，并在联合药物治疗中显示出潜在的协同作用，确定天然化合物为潜在的抗肿瘤药物。植物来源的天然化合物是多种疾病药物的重要来源。例如，突尼斯瑞香科植物在民间医学中用于治疗糖尿病和高血压等不同病症。
评估多毛瑞香提取物的抗肿瘤活性及其在传统结直肠癌治疗中可作为佐剂的潜力。
采用真空液相色谱法对植物叶片的总甲醇提取物进行分离，得到4个馏分。检测这些馏分对结肠癌细胞的细胞毒性活性。
乙酸乙酯馏分（E2馏分）通过激活半胱天冬酶-3诱导细胞周期停滞和凋亡。E2馏分通过降低整合素α5表达和FAK磷酸化抑制细胞侵袭。此外，E2馏分增强了结肠癌细胞对5-氟尿嘧啶治疗的敏感性。
所选植物多毛瑞香是天然化合物的来源，这些化合物可抑制结肠癌细胞的生长和侵袭，并诱导细胞周期停滞。最有趣的结果是它们在5-氟尿嘧啶联合治疗中具有潜在的协同作用。进一步分析将鉴定出活性化合物，并通过使结肠癌细胞对抗癌药物敏感来证实它们在化疗治疗中的作用。
