Effects of 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone from Syzygium nervosum Seeds on Antiproliferative, DNA Damage, Cell Cycle Arrest, and Apoptosis in Human Cervical Cancer Cell Lines

Molecules. 2022 Feb 9;27(4):1154. doi: 10.3390/molecules27041154.

Abstract

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a natural product derived from Syzygium nervosum A. Cunn. ex DC., was investigated for its inhibitory activities against various cancer cell lines. In this work, we investigated the effects of DMC and available anticervical cancer drugs (5-fluorouracil, cisplatin, and doxorubicin) on three human cervical cancer cell lines (C-33A, HeLa, and SiHa). DMC displayed antiproliferative cervical cancer activity in C-33A, HeLa, and SiHa cells, with IC50 values of 15.76 ± 1.49, 10.05 ± 0.22, and 18.31 ± 3.10 µM, respectively. DMC presented higher antiproliferative cancer activity in HeLa cells; therefore, we further investigated DMC-induced apoptosis in this cell line, including DNA damage, cell cycle arrest, and apoptosis assays. As a potential anticancer agent, DMC treatment increased DNA damage in cancer cells, observed through fluorescence inverted microscopy and a comet assay. The cell cycle assay showed an increased number of cells in the G0/G1 phase following DMC treatment. Furthermore, DMC treatment-induced apoptosis cell death was approximately three- to four-fold higher compared to the untreated group. Here, DMC represented a compound-induced apoptosis for cell death in the HeLa cervical cancer cell line. Our findings suggest that DMC, a phytochemical agent, is a potential candidate for antiproliferative cervical cancer drug development.

Keywords: 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone; Syzygium nervosum; antiproliferative cervical cancer activity; chalcone derivative; compound-induced apoptosis.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Cycle Checkpoints / drug effects*
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • DNA Damage*
  • Female
  • HeLa Cells
  • Humans
  • Seeds / chemistry*
  • Syzygium / chemistry*
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / metabolism

Substances

  • 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone
  • Antineoplastic Agents, Phytogenic
  • Chalcones