Haffez Hesham, Sanad Hend H, Ebrahim Hassan, Hassan Zeineb A
Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Cairo, 11795, Egypt.
Center of Scientific Excellence "Helwan Structural Biology Research, (HSBR)", Helwan University, Cairo, 11795, Egypt.
Sci Rep. 2025 May 8;15(1):16102. doi: 10.1038/s41598-025-99616-2.
Cancer is a significant global disease with high mortality and limited therapeutic options. Chemotherapy is a cancer treatment option; however, there are still issues, including severe side effects, inadequate response, and drug resistance. Abietic acid is a natural diterpene with diverse pharmacological properties and can be used for cancer treatment. Therefore, this study aimed to assess the anticancer efficacy of abietic acid in combination with doxorubicin, a highly clinically used chemotherapeutic agent. Biochemical investigations include initial viability assays, combination therapy using isobologram analysis, apoptosis and cell cycle assays, gene expression assay, ELISA analysis of protein expression, DNA fragmentation, and wound healing assays. The data showed that doxorubicin-abietic acid (DOX-AB) is an effective and safe anticancer combination for Caco-2 cells. DOX-AB had a high safety index with minimal cytotoxicity at the combination dose on normal WI-38 fibroblasts cells. DOX-AB significantly decreased the proliferation and viability of Caco-2 cells, with an increase in the apoptosis rate in the late stage and necrosis with cell cycle arrest at the G/M phase. Significant changes in the expression of modulators related to apoptosis, inflammation, and epigenetics were observed in gene and protein levels. DOX-AB combination had more efficient anticancer activity than doxorubicin alone. This study suggested that the use of abietic acid in combination with doxorubicin is a promising treatment for colorectal cancer because it enhances doxorubicin activity at relatively low doses with minimal cytotoxicity and overcomes multidrug resistance in tumors; these findings merit further investigation.
癌症是一种全球性重大疾病，死亡率高且治疗选择有限。化疗是一种癌症治疗方法；然而，仍然存在一些问题，包括严重的副作用、疗效不佳和耐药性。枞酸是一种具有多种药理特性的天然二萜，可用于癌症治疗。因此，本研究旨在评估枞酸与阿霉素（一种临床广泛使用的化疗药物）联合使用的抗癌疗效。生化研究包括初始活力测定、使用等效线图分析的联合治疗、凋亡和细胞周期测定、基因表达测定、蛋白质表达的酶联免疫吸附测定分析、DNA片段化和伤口愈合测定。数据表明，阿霉素 - 枞酸（DOX - AB）对Caco - 2细胞是一种有效且安全的抗癌组合。DOX - AB在联合剂量下对正常WI - 38成纤维细胞具有高安全指数且细胞毒性最小。DOX - AB显著降低了Caco - 2细胞的增殖和活力，后期凋亡率增加，细胞周期在G/M期停滞并出现坏死。在基因和蛋白质水平观察到与凋亡、炎症和表观遗传学相关的调节因子表达有显著变化。DOX - AB联合用药比单独使用阿霉素具有更有效的抗癌活性。本研究表明，枞酸与阿霉素联合使用对结直肠癌是一种有前景的治疗方法，因为它能在相对低剂量下增强阿霉素活性，细胞毒性最小，并克服肿瘤的多药耐药性；这些发现值得进一步研究。
