Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, India.
J Biochem Mol Toxicol. 2022 Apr;36(4):e22999. doi: 10.1002/jbt.22999. Epub 2022 Feb 26.
Pulmonary cancer confronts the greatest hurdle of resistance against most chemotherapeutic drugs. This may be circumvented with a combination of conventional chemotherapy with bioactive herbal adjuvant. Epigallocatechin-3-gallate (EGCG), was investigated for its chemo-sensitizing property along with doxorubicin (Dox), in an intrinsically nonresponsive lung adenocarcinoma (LAC) cell line, A549. A compromised functionality of Dox was reversed when EGCG was used as an adjuvant. On one hand, Dox (10 μM)-EGCG (0.5 μM) post treatment combination decreased the drug efflux, multidrug-resistance (MDR) signaling, invasiveness while, on the other hand, it increased drug internalization, cell-cycle arrest, stress-induced damage, and finally cell death. The resistant nature of A549 was probably due to constitutive activation of nuclear erythroid 2-related factor 2 (Nrf2) and its upstream/downstream antioxidant effectors, which were also pro-oxidatively coordinated by EGCG. In conclusion low dose EGCG improved Dox-toxicity and imparted oxidative damage-mediated antineoplastic efficacy by reorienting the redox signaling in A549 LAC cells.
肺癌面临着对大多数化疗药物产生耐药性的最大障碍。这可以通过将常规化疗与生物活性草药辅助剂联合来规避。儿茶素-3-没食子酸酯 (EGCG) 与多柔比星 (Dox) 一起用于内在无反应性肺腺癌 (LAC) 细胞系 A549 中，研究其化疗增敏特性。当 EGCG 用作佐剂时，Dox 的功能受损得到逆转。一方面，Dox（10μM）-EGCG（0.5μM）治疗后联合用药降低了药物外排、多药耐药 (MDR) 信号、侵袭性，另一方面，它增加了药物内化、细胞周期停滞、应激诱导的损伤，最终导致细胞死亡。A549 的耐药性可能是由于核红细胞 2 相关因子 2 (Nrf2) 的组成性激活及其上游/下游抗氧化效应物，EGCG 也通过这些效应物进行促氧化协调。总之，低剂量 EGCG 通过重新定向 A549 LAC 细胞中的氧化还原信号，提高了 Dox 的毒性，并赋予了氧化损伤介导的抗肿瘤功效。
