The Genome Biology Laboratory, Department of Biosciences, Ramanujan Block, Jamia Millia Islamia, Jamia Nagar, New Delhi, Delhi 110025, India.
Oncol Rep. 2022 Jan;47(1). doi: 10.3892/or.2021.8215. Epub 2021 Nov 5.
Colon cancer is one of the most commonly diagnosed malignancies, which begins as a polyp and grows to become cancer. Diosmin (DS) and naringenin (NR) are naturally occurring flavonoids that exhibit various pharmacological activities. Although several studies have illustrated the effectiveness of these flavonoids as anti‑cancerous agents individually, the combinatorial impact of these compounds has not been explored. In the present study, the combined effect of DS and NR (DiNar) in colon cancer cell lines HCT116 and SW480 were assessed by targeting apoptosis and inflammatory pathways. The MTT assay was used to evaluate the effect of DiNar on cell proliferation, while Chou‑Talalay analysis was employed to determine the combination index of DS and NR. Moreover, flow cytometry was used to monitor cell cycle arrest and population study. The onset of apoptosis was assessed by DAPI staining, DNA fragmentation, and Annexin V‑fluorescein isothiocyanate/propidium iodide (Annexin V‑FITC/PI). The expression levels of apoptotic pathway markers, Bcl‑2, Bax, caspase3, caspase8, caspase9 and p53, and inflammatory markers, NF‑κβ, IKK‑α and IKK‑β, were assessed using western blotting and reverse transcription‑quantitative PCR. These results suggested that DiNar treatment acts synergistically and induces cytotoxicity with a concomitant increase in chromatin condensation, DNA fragmentation and cell cycle arrest in the G0/G1 phase. Annexin V‑FITC/PI apoptosis assay also showed increased number of cells undergoing apoptosis in the DiNar treatment group. Furthermore, the expression of apoptosis and inflammatory markers was also more effectively regulated under the DiNar treatment. Thereby, these findings demonstrated that DiNar treatment could be a potential novel chemotherapeutic alternative in colon cancer.
结肠癌是最常见的恶性肿瘤之一，它起源于息肉并发展为癌症。地奥司明（DS）和柚皮苷（NR）是天然存在的类黄酮，具有多种药理活性。尽管有几项研究表明这些类黄酮作为抗癌剂具有单独的有效性，但这些化合物的组合影响尚未得到探索。在本研究中，通过靶向凋亡和炎症途径，评估了 DS 和 NR（DiNar）联合应用于结肠癌细胞系 HCT116 和 SW480 的效果。MTT 法用于评估 DiNar 对细胞增殖的影响，而 Chou-Talalay 分析用于确定 DS 和 NR 的组合指数。此外，流式细胞术用于监测细胞周期停滞和群体研究。通过 DAPI 染色、DNA 片段化和 Annexin V-荧光素异硫氰酸酯/碘化丙啶（Annexin V-FITC/PI）评估细胞凋亡的发生。使用 Western blot 和逆转录定量 PCR 评估凋亡途径标志物 Bcl-2、Bax、caspase3、caspase8、caspase9 和 p53 以及炎症标志物 NF-κβ、IKK-α 和 IKK-β 的表达水平。这些结果表明，DiNar 处理具有协同作用，并诱导细胞毒性，同时伴有染色质浓缩、DNA 片段化和细胞周期停滞在 G0/G1 期增加。Annexin V-FITC/PI 凋亡测定也显示 DiNar 处理组中有更多的细胞发生凋亡。此外，凋亡和炎症标志物的表达也在 DiNar 处理下得到更有效的调节。因此，这些发现表明 DiNar 处理可能是结肠癌的一种潜在新型化疗替代方法。
