Article Data

  • Views 2572
  • Dowloads 148

Original Research

Open Access

Pterostilbene induces apoptosis through caspase activation in ovarian cancer cells

  • J. Dong1
  • H. Guo1
  • Y. Chen2,*,

1Department of Gynaecology and Obstetrics, Xiangyang Hospital Affiliated with Hubei University of Medicine, Xiangyang, China

2Department of Gynaecology and Obstetrics, People's Hospital, Changyyi, China

DOI: 10.12892/ejgo3024.2016 Vol.37,Issue 3,June 2016 pp.342-347

Published: 10 June 2016

*Corresponding Author(s): Y. Chen E-mail: chenyuhua188@gmail.com

PDF (669.31 kB) View Full-text

Abstract

Aim: Pterostilbene, an analog of resveratrol increasing bioavailability has shown to offer antioxidant and anticancer properties in vitro and in vivo. Dietary compounds with anti-oxidant properties have been shown to gain importance due to therapeutic applications. In addition, compounds with higher bioavailability levels show great interest in present scenario. Thus, the present study aimed at investigating the cytotoxic role of pterostilbene and its mechanism of cell death in ovarian cancer cells line. Materials and Methods: The effect of pterostilbene was determined on SKOV-3 cells, by cytotoxicity assays, oxidative stress levels, [Ca2+]i levels, mitochondrial depolarization, cell cycle analysis and caspase 3, 8, and 9 activities. Results: The study revealed that pterostilbene offered cytotoxic effect at a concentration of IC50-55 uM. Further, pterostilbene induced reactive oxygen species (ROS) mediated intrinsic pathway of apoptosis through enhancing oxidative stress, [Ca2+]i levels, mitochondrial depolarization, Sub G1 accumulation, and activation of caspase 3 and 9. Conclusion: The study demonstrates for the first time the cytotoxic potential of pterostilbene against ovarian cancer cells.

Keywords

Anticancer; ROS; Oxidative stress; Caspase.

Cite and Share

J. Dong, H. Guo, Y. Chen. Pterostilbene induces apoptosis through caspase activation in ovarian cancer cells. European Journal of Gynaecological Oncology. 2016; 37(3): 342-347. doi: 10.12892/ejgo3024.2016

References

[1] Kapetanovic I.M., Muzzio M., Huang, Z., Thompson T.N., Mc- Cormick D.L.: “Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats”. Cancer Chemoth. Pharm., 2011, 68, 593.

[2] Pari L., Satheesh M.A.: “Effect of pterostilbene on hepatic key enzymes of glucose metabolism in streptozotocin- and nicotinamideinduced diabetic rats”. Life Sci., 2006, 79, 641

[3] Rimando A.M., Kalt W., Magee J.B., Dewey J., Ballington J.R.: “Resveratrol, pterostilbene, and piceatannol in Vaccinium berries”. J. Agric. Food Chem., 2004, 52, 4713.

[4] Rimando A.M., Cuendet M., Desmarchelier C., Mehta R.G., Pezzuto J.M., Duke S.O.: “Cancer Chemo-preventive and antioxidant activities of pterostilbene, a naturally occurring analogue of resveratrol”. J. Agric. Food Chem., 2002, 50, 3453.

[5] McCormack D., McFadden D.: “Pterostilbene and cancer: current review”. J. Surg. Res., 2012, 173, 53.

[6] Remsberg C.M., Yáñez J.A., Ohgami Y., Vega-Villa K.R., Rimando A.M., Davies N.M.: “Pharmacometrics of pterostilbene: preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity”. Phytother. Res., 2008, 22, 169.

[7] Pan M.H., Ho C.T.: “Chemopreventive effects of natural dietary compounds on cancer development”. Chem. Soc. Rev., 2008, 37, 2558.

[8] Pan M.H., Ghai G., Ho C.T.: “Food bioactives, apoptosis, and cancer”. Mol. Nutr. Food Res., 2008, 52, 43.

[9] Pan M.H., Chang Y.H., Badmaev V., Nagabhushanam K., Ho C.T.: “Pterostilbene induces apoptosis and cell cycle arrest in human gastric carcinoma cells”. J. Agric. Food Chem., 2007, 55, 7777.

[10] Alosi J.A., McDonald D.E., Schneider J.S., Privette A.R., McFadden D.W.: “Pterostilbene inhibits breast cancer in vitro through mitochondrial depolarization and induction of caspase-dependent apoptosis”. J. Surg. Res., 2010, 161, 195.

[11] Schneider J.G., Alosi J.A., McDonald D.E., McFadden D.W.: “Pterostilbene inhibits lung cancer through induction of apoptosis”. J. Surg. Res., 2010, 161, 18.

[12] Mannal P., McDonald D., McFadden D.: “Pterostilbene and tamoxifen show an additive effect against breast cancer in vitro”. Am. J. Surg., 2010, 200, 577.

[13] Chen R.J., Ho C.T., Wang Y.J.: “Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells”. Mol. Nutr. Food Res., 2010, 54, 1819.

[14] Wang Y., Ding L., Wang X., Zhang J., Han W., Feng L., et al.: “Pterostilbene simultaneously induces apoptosis, cell cycle arrest and cyto-protective autophagy in breast cancer cells”. Am. J. Transl. Res., 2012, 4, 44

[15] Mossman T: “Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays”. J. Immunol. Methods, 1983, 65, 55.

[16] Stuehr D.J., Marletta M.A.: “Induction of Nitrite and nitrate synthesis in murine macrophage by Bchinfection, limbokines, or interferongamma”. Immuno., 1987, 139, 518.

[17] Royall J.A., Ischiropoulos H.: “Evaluation of 2,7-dichlorofluorescein and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells”. Arch. Biochem. Biophy., 1993, 302, 348.

[18] Erel O.: “Novel automated method to measure total antioxidant response against potent free radical reactions”. Clin. Biochem., 2004, 37, 112.

[19] Nutakul W., Sobers H.S., Qiu P., Dong P., Decker E.A., McClements D.J., Xiao H.: “Inhibitory effects of resveratrol and pterostilbene on human colon cancer cells: a side-by-side comparison”. J. Agric. Food Chem., 2011, 59, 10964.

[20] Dong P., Qiu P., Zhu Y., Li S., Ho C.T., Xiao H.: “Simultaneous Determination of Four 5-Hydroxy Polymethoxyflavones by reversedphase high performance liquid chromatograph with electrochemical detection”. J. Chromatogr. A., 2010, 1217, 642.

[21] Okhawa H., Olishi N., Yasi K.: “Assay for lipid peroxides in animal tissues by thiobarbutric acid reaction”. Biochem., 1979, 95, 351.

[22] Tusi S.K., Khalaj L., Ashabi G., Kiaei M., Khodagholi F.: “Alginate oligosaccharide protects against endoplasmic reticulum and mitochondrial mediated apoptotic cell death and oxidative stress”. Biomaterials, 2011, 32, 438.

[23] Langmar Z., Németh M., Vlesko G., Király M., Hornyák L., Bösze P.: “HE4–a novel promising serum marker in the diagnosis of ovarian carcinoma”. Eur. J. Gynaecol. Oncol., 2011, 32, 605.

[24] Mena S., Rodríguez M.L., Ponsoda X., Estrela J.M., Jaattela M., Ortega A.L.: “Pterostilbene-induced tumor cytotoxicity: a lysosomal membrane permeabilization-dependent mechanism”. PLoS One, 2011, 7, 445.

[25] Autréaux B.D., Toledano M.B.: “ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis Apoptosis”. Nat. Rev. Mol. Cell. Biol., 2007, 8, 813.

[26] Vaz M., Machireddy N., Irving A., Potteti H.R., Chevalier K., Kalvakolanu D., Reddy S.P.: “Oxidant-induced cell death and Nrf2- dependent antioxidative response are controlled by Fra-1/AP-1”. Mol. Cell. Biol., 2012, 32, 1694.

[27] Hasiah A.H., Ghazali A.R., Weber J.F., Velu S., Thomas N.F., Inayat Hussain S.H.: “Cytotoxic and antioxidant effects of methoxylated stilbene analogues on HepG2 hepatoma and Chang liver cells: implicationsfor structure activity relationship”. Hum. Exp. Toxicol., 2 011,30, 138.

[28] Ly J.D., Grubb, D.R., Lawen A.: “The mitochondrial membrane potential (Δψm) in apoptosis; an update”. Apop., 2003, 8, 115.

[29] Duchen M.R.: “Mitochondria and calcium: from cell signalling to cell death”. J. Physiol., 2000, 1, 57.

[30] Chakraborty A., Gupta N., Ghosh K., Roy P.: “In vitro evaluation of the cytotoxic, anti-proliferative and anti-oxidant properties of pterostilbene isolated from Pterocarpus marsupium”. Toxicol. In Vitro, 2010, 24, 1215.

[31] Lin V.C., Tsai Y.C., Lin J.N., Fan L.L., Pan M.H., Ho C.T., et al.: “Activation of AMPK by pterostilbene suppresses lipogenesis and cell-cycle progression in p53 positive and negative human prostate cancer cells”. J. Agri. Food Chem., 2012, 60, 6399.

[32] Riedl S.J., Shi Y.: “Molecular mechanisms of caspase regulation during apoptosis”. Nat. Rev. Mol. Cell. Biol., 2004, 5, 897.

[33] Mannal PW, Alosi JA, Schneider JG, McDonald DE, McFadden DW. “Pterostilbene inhibits pancreatic cancer in vitro”. J. Gastrointest. Surg., 2010, 14, 873.

[34] McCormack D.E., Mannal P., McDonald D., Tighe S., Hanson J., McFadden D.: “Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo”. J. Gastrointes. Surg., 2012, 16, 1136.

[35] Moon D., McCormack D., McDonald D., McFadden D.: “Pterostilbene induces mitochondrially derived apoptosis in breast cancer cells in vitro”. J. Surg. Res., 2013, 180, 208.

Submission Turnaround Time

Top