Kaempferol Induces Cell Death and Sensitizes Human Head and Neck Squamous Cell Carcinoma Cell Lines to Cisplatin

Adv Exp Med Biol. 2021:1326:95-109. doi: 10.1007/5584_2020_603.

Abstract

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.

Keywords: 3,5,7-Trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one; Cisplatin and sensitization; Kaempferol; Mitochondria; Oral Cancer.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis
  • Carcinoma, Squamous Cell* / drug therapy
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Head and Neck Neoplasms* / drug therapy
  • Humans
  • Kaempferols / pharmacology
  • Kaempferols / therapeutic use
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / genetics

Substances

  • Antineoplastic Agents
  • Kaempferols
  • Cisplatin