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Kaempferitrin induces apoptosis via intrinsic pathway in HeLa cells and exerts antitumor effects
Authors:Angel Josabad Alonso-Castro  Elizabeth Ortiz-Sánchez  Alejandro García-Regalado  Graciela Ruiz  José Martín Núñez-Martínez  Ignacio González-Sánchez  Valeria Quintanar-Jurado  Elizabeth Morales-Sánchez  Fabiola Dominguez  Gabriela López-Toledo  Marco A Cerbón  Alejandro García-Carrancá
Institution:1. Facultad de Química Universidad Nacional Autónoma de México, Mexico;2. Unidad de Investigación Básica, Instituto Nacional de Cancerología, Mexico;3. Universidad Autónoma Metropolitana campus Cuajimalpa, Mexico;4. Universidad Autónoma Metropolitana campus Xochimilco, Mexico;5. Unidad de Validación de Biomarcadores, Instituto Nacional de Medicina Genómica, Mexico;6. Centro de Investigación Biomédica de Oriente, IMSS, Metepec, Puebla, Mexico;g Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico
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.
Keywords:(CDDP)  Cisplatin  (CM-H2DCFDA)  5-(and-6)-carboxy-2&prime    7&prime  -dichlorodihydrofluorescein diacetate  (DMEM)  Dulbecco's modified Eagle's medium  (DMSO)  Dimethyl sulfoxide  (EDTA)  Ethylenediaminetetraacetic acid  (FBS)  Fetal bovine serum  (HRP)  Horseraplate peroxidase  (KM)  Kaempferitrin  (MTT)  3-(4  5-dimethylthiazol-2-yl)-2  5-diphenyltetrazolium bromide  (PBS)  Phosphate buffer solution  (PCX)  Paclitaxel  (ROS)  Reactive oxygen species  (TUNEL)  Terminal deoxynucleotidyl transferase dUTP nick end labeling
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