Clinical and Molecular Pharmacology Program, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Institute for Research in Dental Sciences (ICOD), Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
Adv Exp Med Biol. 2021;1326:95-109. doi: 10.1007/5584_2020_603.
Cisplatin is a first-line chemotherapeutic drug commonly used to treat patients with head and neck cancer; nevertheless, cisplatin resistance poses a main challenge for its clinical efficacy. Recent studies have shown that kaempferol, a natural flavonoid found in various plants and foods, has an anticancer effect. The following study evaluated the cytotoxic effects of kaempferol on head and neck tumor cells and their mechanism of action, evaluating the effects on proliferation, the oxygen consumption rate, transmembrane potential, tumor cell migration and induction of apoptosis. Moreover, we determined the effects of a combination of kaempferol and cisplatin on head and neck tumor cells. We found that kaempferol inhibited the oxygen consumption rate and decreased the intracellular ATP content in tumor cells. This novel mechanism may inhibit the migratory capacity and promote antiproliferative effects and apoptosis of tumor cells. Additionally, our in vitro data indicated that kaempferol may sensitize head and neck tumor cells to the effects of cisplatin. These effects provide new evidence for the use of a combination of kaempferol and cisplatin in vivo and their future applications in head and neck cancer therapy.
顺铂是一种常用的一线化疗药物,用于治疗头颈部癌症患者;然而,顺铂耐药性是其临床疗效的主要挑战。最近的研究表明,山奈酚是一种存在于多种植物和食物中的天然类黄酮,具有抗癌作用。本研究评估了山奈酚对头颈部肿瘤细胞的细胞毒性作用及其作用机制,评估了对增殖、耗氧量、跨膜电位、肿瘤细胞迁移和诱导细胞凋亡的影响。此外,我们还确定了山奈酚与顺铂联合应用对头颈部肿瘤细胞的影响。我们发现山奈酚抑制了肿瘤细胞的耗氧量并降低了细胞内 ATP 含量。这种新的机制可能抑制了肿瘤细胞的迁移能力,促进了增殖抑制和细胞凋亡。此外,我们的体外数据表明,山奈酚可能使头颈部肿瘤细胞对顺铂的作用敏感。这些作用为体内联合使用山奈酚和顺铂提供了新的证据,并为其在头颈部癌症治疗中的未来应用提供了依据。