Raina Ritu, Hussain Arif, Almutary Abdulmajeed G, Haque Shafiul, Raza Tasleem, D'Souza Ashley Cletus, Subramani Sachin, Sajeevan Akash
School of Life Sciences, Manipal Academy of Higher of Education, Academic City 345050, Dubai, United Arab Emirates.
Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Khalifa City, Abu Dhabi 51072, United Arab Emirates.
ACS Omega. 2023 Oct 27;8(44):41204-41213. doi: 10.1021/acsomega.3c04443. eCollection 2023 Nov 7.
Combinational treatment is a promising strategy for better cancer treatment outcomes. Chrysin and luteolin have demonstrated effective anticancer activity. Cisplatin and topotecan are commonly used for the treatment of human cancers. However, various side effects including drug resistance are an imperative restriction to use them as pharmacological therapy. Therefore, the aim was to use these agents in combination with flavones for better efficacy. In the present study, it was found that the combination of chrysin and cisplatin and luteolin and cisplatin significantly improved the anticancer effect as both the combinations showed synergistic interactions [combinational index (CI < 1)]. Remarkably, the combination of chrysin and luteolin with topotecan depicted the antagonistic interaction (CI > 1). Further, increased expression of the pro-apoptotic proteins Bax and caspase 8 and the inhibition of the antiapoptotic protein Bcl-2 were instituted in the synergistic doses (chrysin + cisplatin and luteolin + cisplatin), hence promoting apoptosis. Also, it was found that the synergistic combination inhibited the migration of HeLa cells by downregulation of metalloproteases and upregulation of TIMPs. However, there are no significant changes depicted in the antagonistic combinations which support their role in their antagonistic effects. Based on these results, it can be inferred that the two or more drug combinations need to be explored well for their interaction to enhance the therapeutic outcomes.
联合治疗是一种有望改善癌症治疗效果的策略。白杨素和木犀草素已显示出有效的抗癌活性。顺铂和拓扑替康常用于治疗人类癌症。然而，包括耐药性在内的各种副作用是将它们用作药物治疗的一个迫切限制。因此，目的是将这些药物与黄酮类化合物联合使用以提高疗效。在本研究中，发现白杨素与顺铂以及木犀草素与顺铂的组合显著提高了抗癌效果，因为这两种组合均显示出协同相互作用[联合指数(CI<1)]。值得注意的是，白杨素和木犀草素与拓扑替康的组合表现出拮抗相互作用(CI>1)。此外，在协同剂量组(白杨素+顺铂和木犀草素+顺铂)中，促凋亡蛋白Bax和半胱天冬酶8的表达增加，抗凋亡蛋白Bcl-2受到抑制，从而促进了细胞凋亡。同时，还发现协同组合通过下调金属蛋白酶和上调金属蛋白酶组织抑制因子来抑制HeLa细胞的迁移。然而，拮抗组合中未显示出显著变化，这支持了它们在拮抗作用中的作用。基于这些结果，可以推断需要对两种或更多种药物组合的相互作用进行充分探索，以提高治疗效果。
