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Article

SB365, Pulsatilla Saponin D Induces Caspase-Independent Cell Death and Augments the Anticancer Effect of Temozolomide in Glioblastoma Multiforme Cells

1
Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Korea
2
Department of Biomedical Laboratory Science, Cheongju University, Cheongju 28503, Korea
3
Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Roberto Fabiani
Molecules 2019, 24(18), 3230; https://doi.org/10.3390/molecules24183230
Received: 8 August 2019 / Revised: 2 September 2019 / Accepted: 4 September 2019 / Published: 5 September 2019
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
SB365, a saponin D extracted from the roots of Pulsatilla koreana, has been reported to show cytotoxicity in several cancer cell lines. We investigated the effects of SB365 on U87-MG and T98G glioblastoma multiforme (GBM) cells, and its efficacy in combination with temozolomide for treating GBM. SB365 exerted a cytotoxic effect on GBM cells not by inducing apoptosis, as in other cancer cell lines, but by triggering caspase-independent cell death. Inhibition of autophagic flux and neutralization of the lysosomal pH occurred rapidly after application of SB365, followed by deterioration of mitochondrial membrane potential. A cathepsin B inhibitor and N-acetyl cysteine, an antioxidant, partially recovered cell death induced by SB365. SB365 in combination with temozolomide exerted an additive cytotoxic effect in vitro and in vivo. In conclusion, SB365 inhibits autophagic flux and induces caspase-independent cell death in GBM cells in a manner involving cathepsin B and mainly reactive oxygen species, and its use in combination with temozolomide shows promise for the treatment of GBM. View Full-Text
Keywords: Pulsatilla saponin D; SB365; glioblastoma multiforme; temozolomide; autophagic flux inhibition; lysosomal membrane permeabilization; mitochondrial membrane potential Pulsatilla saponin D; SB365; glioblastoma multiforme; temozolomide; autophagic flux inhibition; lysosomal membrane permeabilization; mitochondrial membrane potential
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MDPI and ACS Style

Hong, J.-M.; Kim, J.-H.; Kim, H.; Lee, W.J.; Hwang, Y.-i. SB365, Pulsatilla Saponin D Induces Caspase-Independent Cell Death and Augments the Anticancer Effect of Temozolomide in Glioblastoma Multiforme Cells. Molecules 2019, 24, 3230. https://doi.org/10.3390/molecules24183230

AMA Style

Hong J-M, Kim J-H, Kim H, Lee WJ, Hwang Y-i. SB365, Pulsatilla Saponin D Induces Caspase-Independent Cell Death and Augments the Anticancer Effect of Temozolomide in Glioblastoma Multiforme Cells. Molecules. 2019; 24(18):3230. https://doi.org/10.3390/molecules24183230

Chicago/Turabian Style

Hong, Jun-Man, Jin-Hee Kim, Hyemin Kim, Wang J. Lee, and Young-il Hwang. 2019. "SB365, Pulsatilla Saponin D Induces Caspase-Independent Cell Death and Augments the Anticancer Effect of Temozolomide in Glioblastoma Multiforme Cells" Molecules 24, no. 18: 3230. https://doi.org/10.3390/molecules24183230

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