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Open AccessArticle

Gardenia jasminoides Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes

1
Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
2
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
3
Department of Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
*
Authors to whom correspondence should be addressed.
Nutrients 2020, 12(1), 196; https://doi.org/10.3390/nu12010196
Received: 24 December 2019 / Revised: 5 January 2020 / Accepted: 7 January 2020 / Published: 10 January 2020
(This article belongs to the Special Issue Flavonoids and Cancer Prevention)
Gliomas are the most observed primary brain tumor, of which glioblastoma multiform (GBM) shows the highest incidence. Radiotherapy with temozolomide is the standard therapeutic method, but because of side effects, search for alternative therapies is required. Gardenia jasminoides (GJ) is flavonoid abundant with beneficial effects on inflammation, metabolic diseases, and cancers. In this study, we investigated the synergistic combination of GJ and cisplatin (CDDP) in U87MG and U373MG GBM cells. GJ and CDDP both showed cytotoxicity in U87MG cells, however GJ did not affect viability of normal astrocytes while CDDP displayed high toxicity. Cytotoxic effect of GJ and CDDP was related in apoptosis when confirmed by Western blot assays on cleaved caspase-3, caspase-9, and PARP. Moreover, GJ and CDDP showed synergistic combination in cell death of GBM cells, which was further confirmed by Western blot assays of apoptosis factors and also flow cytometry of Annexin V. Analysis on autophagy factors showed that GJ/CDDP combination induced autophagy, and through inhibition of autophagy, we could confirm autophagy is crucial to cytotoxicity of GJ/CDDP in GBM cell lines. The autophagy-mediated apoptosis of GJ/CDDP was dependent on the AKT/mTOR pathway. Overall, our results suggest GJ/CDDP combination as an effective yet safe therapeutic approach to GBMs. View Full-Text
Keywords: glioblastoma; Gardenia jasminoides; cisplatin (CDDP); synergy; apoptosis; autophagy; AKT/mTOR pathway glioblastoma; Gardenia jasminoides; cisplatin (CDDP); synergy; apoptosis; autophagy; AKT/mTOR pathway
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Kim, H.I.; Hong, S.H.; Ku, J.M.; Kim, M.J.; Ju, S.W.; Chang, S.W.; Cheon, C.; Ko, S.-G. Gardenia jasminoides Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes. Nutrients 2020, 12, 196.

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