Cucurbitacin IIb from Ibervillea sonorae Induces Apoptosis and Cell Cycle Arrest via STAT3 Inhibition

Author:

Torres-Moreno Heriberto1,Marcotullio Maria C.2,Velazquez Carlos1,Arenas-Luna Víctor M.3,Hernández-Gutiérrez Salomón3,Robles-Zepeda Ramón E.1ORCID

Affiliation:

1. Departamento de Ciencias Quimico Biologicas, Universidad de Sonora, Blvd. Luis Encinas y Rosales, Hermosillo, Sonora 83000, Mexico

2. Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Perugia – Via del Liceo, 1, 06123 Perugia, Italy

3. Molecular Biology Laboratory, School of Medicine, Universidad Panamericana, Augusto Rodin 498, Benito Juarez, 03920 Insurgentes Mixcoac, MEX, Mexico

Abstract

Background: Cucurbitacin IIb (CIIb) from Ibervillea sonorae has a high capacity to suppress cancer cell proliferation and induce apoptosis. This study investigated the molecular mechanisms related to the antiproliferative and apoptosis induction capacity of CIIb in HeLa cells. Materials and Methods: The cell viability and anti-proliferative effect of CIIb were evaluated by using the trypan blue exclusion assay. The effect of CIIb on the mitochondrial membrane potential was determined by flow cytometry using JC-1. The activity of caspase-3 and caspase-9 was evaluated by flow cytometry using commercial kits. The effect of CIIb on the cell cycle was investigated using Fluorescence-Activated Cell Sorting (FACS) analysis. Western blot analysis was used to evaluate both the inhibitory effect of CIIb on the STAT3 signaling pathway and cyclin –B1, and DNA damage by the comet assay. Results: CIIb triggers disruption of the mitochondrial membrane potential (Δψm) and consequently activated the caspases -3 and -9, as a result of the activation of the intrinsic pathway of the apoptosis. Likewise, the CIIbinduced cell cycle was arrested in S and G2/M after 24h of treatment. CIIb also reduced the expression of STAT3 and cyclin –B1. Finally, CIIb produced an antiproliferative effect at 48 and 72 h, inducing DNA damage. Conclusion: These results demonstrate CIIb-induced apoptosis and cell cycle arrest in HeLa through the inhibition of STAT3.

Funder

National Council for Science and Technology of Mexico

Publisher

Bentham Science Publishers Ltd.

Subject

Cancer Research,Pharmacology,Molecular Medicine

Reference44 articles.

1. Lee, W.C.; Kopetz,S.; Wistuba, I.I.Z.J. Metastasis of cancer: When and how? Ann. Oncol. 2017,28,2045-2047. http://dx.doi.org/10.1093/annonc/mdx327

2. Chen, D.H.; Zhang, X.S. Targeted therapy: Resistance and re-sensitization. Chin, J. Cancer. 2015,34(11),496-501. PMID: 26370727

3. Faqi.; A.S. A Comprehensive Guide to Toxicology in Preclinical Drug Development, 1st ed; Academia Press: New York. 2013.

4. Silva, I.T.; Carvalho,A.; Lang, K.L.; Dudek, S.E.; Masemann,D.; Durán, F.J.; Caro, M.S.B.; Rapp, U.R.; Wixler,V.; Schenkel, E.P.; Simões, C.M.O.; Ludwig, S. In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B. PLoS One. 2015,10(2),e0117794. http://dx.doi.org/10.1371/journal.pone.0117794 PMID: 25674792

5. Kim, S.R.; Seo, H.S.; Choi, H.S.; Cho, S.G.; Kim, Y.K.; Hong, E.H.; Shin, Y.C.; Ko, S.G. Trichosanthes kirilowii ethanol extract and Cucurbitacin D inhibit cell growth and induce apoptosis through inhibition of STAT3 activity in breast cancer cells, J. Evid. Based Complementary Altern. Med. 2013,2013,975350

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