Kaempferitrin induces apoptosis via intrinsic pathway in HeLa cells and exerts antitumor effects

J Ethnopharmacol. 2013 Jan 30;145(2):476-89. doi: 10.1016/j.jep.2012.11.016. Epub 2012 Dec 2.

Abstract

Ethnopharmacological relevance: Justicia spicigera is used for the empirical treatment of cervical cancer in Mexico. Recently, we showed that Justicia spicigera extracts exerted cytotoxic and antitumoral effects and the major component of this extract was kaempferitrin (KM).

Materials and methods: The cytotoxic and apoptotic effect of KM on human cancer cells and human nontumorigenic cells were evaluated using MTT and TUNEL assays, and Annexin V/Propidium iodide detection by flow cytometry. The effect of KM on cell cycle was analyzed by flow cytometry with propidium iodide. The apoptotic and cell cycle effects were also evaluated by western blot analysis. Also, different doses of KM were injected intraperitoneally daily into athymic mice bearing tumors of HeLa cells during 32 days. The growth and weight of tumors were measured.

Results: KM induces high cytotoxic effects in vitro and in vivo against HeLa cells. The general mechanisms by which KM induces cytotoxic effects include: cell cycle arrest in G1 phase and apoptosis via intrinsic pathway in a caspase dependent pathway. Also, KM exerts chemopreventive and antitumor effects.

Conclusion: KM exerts cytotoxic and antitumor effects against HeLa cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclin D1 / metabolism
  • Humans
  • In Situ Nick-End Labeling
  • Kaempferols / pharmacology*
  • Kaempferols / therapeutic use
  • Male
  • Mice
  • Mice, Nude
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phytotherapy
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Ccnd1 protein, mouse
  • Kaempferols
  • Proliferating Cell Nuclear Antigen
  • Reactive Oxygen Species
  • Cyclin D1
  • Proto-Oncogene Proteins c-akt
  • Caspase 3
  • lespenefril