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Cancer Lett. 2019 Feb 28;443:25-33. doi: 10.1016/j.canlet.2018.11.027. Epub 2018 Nov 29.

Isolinderalactone regulates the BCL-2/caspase-3/PARP pathway and suppresses tumor growth in a human glioblastoma multiforme xenograft mouse model.

Author information

1
Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea.
2
Department of Anatomy, College of Medicine, Kosin University, Busan, 49267, Republic of Korea.
3
Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Electronic address: brainsw@gmail.com.
4
Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Electronic address: julie@pusan.ac.kr.

Abstract

Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which remains incurable. Plant extracts are a potential source of potent anticancer medicines. In this study, we investigated the effect of isolinderalactone from Lindera aggregata on tumor growth using U-87 human glioblastoma cells. Treatment with isolinderalactone inhibited cell viability and promoted apoptotic cell death. In addition, intraperitoneal injection of isolinderalactone significantly inhibited tumor growth in a human GBM xenograft mouse model. To identify the proteins involved in the induction of apoptosis in isolinderalactone-treated cells, we performed a human apoptosis proteome array analysis and western blotting. Isolinderalactone suppressed the expression of B-cell lymphoma 2 (BCL-2), as well as of survivin and X-linked inhibitor of apoptosis protein (XIAP), known as apoptosis inhibitors, and increased the level of cleaved caspase-3. In addition, isolinderalactone treatment increased cleaved poly(ADP-ribose) polymerase (PARP) and DNA damage. In xenograft tumor tissues, we observed high immunofluorescence of cleaved caspase-3 and TUNEL in isolinderalactone-treated group. Taken together, isolinderalactone enhances U-87 GBM cell apoptosis in vitro and in vivo and retards tumor growth, suggesting that isolinderalactone may be a potential candidate for anti-glioblastoma drug development.

KEYWORDS:

Brain tumor; Herb extract; Lindera aggregata; Radix Linderae

PMID:
30503550
DOI:
10.1016/j.canlet.2018.11.027
[Indexed for MEDLINE]

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