Kaushik Shweta, Shyam Hari, Sharma Ramesh, Balapure Anil K
Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Taramani, Chennai, Tamil Nadu, India.
Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India; Centre for Advance Research, King George's Medical University, Lucknow, Uttar Pradesh, India.
Indian J Pharmacol. 2016 Nov-Dec;48(6):637-642. doi: 10.4103/0253-7613.194852.
Despite the progress in the diagnosis and treatment of breast cancer, it remains a major health problem in women. Natural flavones along with chemotherapeutic agents enhance therapeutic response and minimize toxicity of chemical agents. Centchroman (CC) colloquially called as ormeloxifene, is a nonsteroidal oral contraceptive categorized as selective estrogen receptor modulator with anti-breast cancer activity. Genistein (GN), an isoflavone found mainly in soy products possesses anti-cancerous potential against a number of cancers including breast. The present study aims at investigating the combination of CC and GN in human breast cancer cell lines (HBCCs).
Cytotoxic effect of CC and GN separately and in combination were assessed by sulforhodamine B (SRB) assay in MDA MB-231, MDA MB-468, MCF-7, T-47D HBCCs, and nontumorigenic human mammary epithelial cell (HMEC) MCF-10A. The drug interaction was analyzed using CompuSyn software through which combination index and dose reduction index were generated.
Combination of CC plus GN exerts significantly higher cytotoxicity compared to each drug in HBCCs, whereas HMEC-MCF-10A remains unaffected.
On an overall basis, the drugs in combination enhanced cell killing in malignant cells. Therefore, the combination of CC with GN may offer a novel approach for the breast cancer.
尽管乳腺癌的诊断和治疗取得了进展,但它仍然是女性的一个主要健康问题。天然黄酮与化疗药物一起可增强治疗反应并使化学药物的毒性最小化。醋甲羟孕酮(CC)俗称奥美昔芬,是一种非甾体类口服避孕药,归类为具有抗乳腺癌活性的选择性雌激素受体调节剂。染料木黄酮(GN)是一种主要存在于豆制品中的异黄酮,对包括乳腺癌在内的多种癌症具有抗癌潜力。本研究旨在研究CC和GN在人乳腺癌细胞系(HBCCs)中的联合作用。
通过磺酰罗丹明B(SRB)法评估CC和GN单独及联合使用对MDA MB - 231、MDA MB - 468、MCF - 7、T - 47D HBCCs以及非致瘤性人乳腺上皮细胞(HMEC)MCF - 10A的细胞毒性作用。使用CompuSyn软件分析药物相互作用,由此生成联合指数和剂量降低指数。
与每种药物单独使用相比,CC加GN的联合用药在HBCCs中具有显著更高的细胞毒性,而HMEC - MCF - 10A不受影响。
总体而言,联合用药增强了对恶性细胞的杀伤作用。因此,CC与GN的联合使用可能为乳腺癌提供一种新的治疗方法。