Department of Biochemistry, All India Institute Medical Sciences (AIIMS), New Delhi-110029, India.
Asian Pac J Cancer Prev. 2023 Nov 1;24(11):3705-3714. doi: 10.31557/APJCP.2023.24.11.3705.
The present study explored the molecular mechanism of herbal (Unani) drug Habb-e-asgandh as anti-tumorigenic adjuvant therapy experimentally in U266 cells and its role in treatment of Multiple myeloma. The formulation of Habb-e-asgandh is investigated alone or as a combinatorial therapy with standard drug lenalidomide to check for its efficacy against U266 myeloma cells for prevention of drug relapse and resistance.
We performed the following assays on singly or in combination of Habb-e-asgandh-Lenalidomide treated U266 cells. The cytotoxicity evaluation done by MTT assay, we studied cell cycle kinetics by Propidium Iodide staining, mitochondrial apoptosis analysis by Annexin V/PI dual staining and JC1 staining assays. Further, anti-oxidative potential was assessed by ORAC assay and cytokine levels estimation of anti-inflammatory (TNF-alpha and IL6) and anti-angiogenic (VEGF and Ang-2) markers were done by ELISA.
The myeloma U266 cells when treated with Habb-e-asgandh alone or in combination with standard drug lenalidomide showed cytotoxicity in dose dependent manner with promising effects at 0.4 mg/ml (IC30) and 1.5 mg/ml (IC50) inhibitory concentrations. The formulation treated cells showed modulation in cell cycle kinetics patterned by sub Go/G1 population accumulation. Furthermore, it induced mitochondrial apoptosis mainly at half maximal inhibitory concentration and in combinatorial combinations. Significantly elevated oxidative capacities (p<0.05) and reduced levels of angiogenic and pro-inflammatory markers were observed. Multiple mechanism based inhibition by Habb-e-asgandh in co-treatment with lenalidomide against myeloma cells is indicated. Conclusion: Habb-e-asgandh formulation possess anti-tumorigenic efficacy against multiple myeloma. The adjunctive Habb-e-asgandh formulation with standard chemotherapeutic drug may prove to be a potent anti-myeloma agent in interventional therapy for Multiple myeloma if further studied in future avenues.
本研究通过 U266 细胞实验探索草药（Unani）药物 Habb-e-asgandh 的分子机制，作为抗肿瘤辅助治疗，并研究其在多发性骨髓瘤治疗中的作用。研究 Habb-e-asgandh 的配方，单独或与标准药物来那度胺联合治疗，以检查其对 U266 骨髓瘤细胞的疗效，防止药物复发和耐药。
我们对单独或联合 Habb-e-asgandh-来那度胺治疗的 U266 细胞进行了以下实验。通过 MTT 测定法评估细胞毒性，通过碘化丙啶染色研究细胞周期动力学，通过 Annexin V/PI 双重染色和 JC1 染色法分析线粒体凋亡。此外，通过 ORAC 测定法评估抗氧化能力，并通过 ELISA 测定抗炎（TNF-α和 IL6）和抗血管生成（VEGF 和 Ang-2）标志物的细胞因子水平。
骨髓瘤 U266 细胞用 Habb-e-asgandh 单独或与标准药物来那度胺联合治疗时，表现出剂量依赖性的细胞毒性，在 0.4mg/ml（IC30）和 1.5mg/ml（IC50）抑制浓度下具有良好的效果。该配方处理的细胞显示出细胞周期动力学的调节，表现为亚 Go/G1 群体的积累。此外，它主要在半最大抑制浓度和组合中诱导线粒体凋亡。显著提高了氧化能力（p<0.05），降低了血管生成和促炎标志物的水平。在与来那度胺联合治疗时，Habb-e-asgandh 表现出多种机制的抑制作用，对骨髓瘤细胞有抑制作用。
Habb-e-asgandh 配方对多发性骨髓瘤具有抗肿瘤疗效。如果在未来的研究中进一步研究，辅助 Habb-e-asgandh 配方与标准化疗药物可能成为多发性骨髓瘤介入治疗的有效抗骨髓瘤药物。
