Cytotoxic Activity of Cambodian Leaves Extract (Plumeria acuminate) on Breast Cancer Cells and COX-2 Targeted Prediction of Its Chemical Contents

Inggita Hasi Rahmah, Hayfa Salsabila Harsan, Faaza Aulia Rahman, E. Meiyanto, R. A. Susidarti
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Abstract

Cambodian leaves are suspected to contain stigma sterol which may target Cyclo-Oxygenase-2 (COX-2) or Estrogen Receptor (ER) to contribute to its cytotoxic activity on breast cancer cells. This study aimed to determine the potential of Cambodian leaf compounds and extracts as chemopreventive agents for luminal breast cancer with a molecular target of COX-2. Ethanol was used to extract the active compound of Cambodian leaves. The study on chemical activity against COX-2 employed molecular docking with Molecular Operating Environment (MOE) and the cytotoxic property of Cambodian leaf extract (CLE) on T47D was determined using the trypan blue exclusion method. The extraction yielded as 4.87% w/w CLE. Thin layer chromatography showed that Cambodian leaves contain sterol. Molecular docking confirmed that several sterol compounds have greater affinity to COX-2 than native ligands indicating that they are potent as COX-2 inhibitors. They are Stigmast-7-en-3-ol, Lupeol Acetate, and Lupeol carboxylic acid with docking scores of -14.3874, -13.8098, and -14.1045 kcal/mol respectively. The CLE exhibited cytotoxic activity on T47D cells with an IC50 value of 18 μg/mL. Therefore, CLE has a potential effect as a chemopreventive agent for breast cancer and potentially as a COX-2 inhibitor.Keywords: Cambodian leaf extract, breast cancer, COX-2 inhibitor, chemopreventive.
柬埔寨叶提取物(渐冻人梅)对乳腺癌细胞的细胞毒活性及其化学成分的 COX-2 靶向预测
柬埔寨树叶被怀疑含有柱头固醇,这种固醇可能以环氧化酶-2(COX-2)或雌激素受体(ER)为靶点,从而对乳腺癌细胞产生细胞毒性作用。本研究旨在确定柬埔寨叶化合物和提取物作为以 COX-2 为分子靶点的腔隙型乳腺癌化学预防剂的潜力。研究使用乙醇提取柬埔寨树叶的活性化合物。针对 COX-2 的化学活性研究采用了分子操作环境(MOE)进行分子对接,并使用胰蓝排除法确定了柬埔寨叶提取物(CLE)对 T47D 的细胞毒性。萃取结果显示,柬埔寨叶提取物对 T47D 的细胞毒性为 4.87%(重量百分比)。薄层色谱法显示柬埔寨叶含有甾醇。分子对接证实,几种甾醇化合物与 COX-2 的亲和力大于原生配体,表明它们是有效的 COX-2 抑制剂。它们是石蒜甾-7-烯-3-醇、醋酸羽扇豆醇和羽扇豆醇羧酸,对接得分分别为-14.3874、-13.8098 和 -14.1045 kcal/mol。CLE 对 T47D 细胞具有细胞毒性活性,IC50 值为 18 μg/mL。因此,CLE具有作为乳腺癌化学预防剂和潜在 COX-2 抑制剂的潜在作用:柬埔寨叶提取物 乳腺癌 COX-2 抑制剂 化学预防
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