Leptospermum extract (QV0) suppresses pleural mesothelioma tumor growth in vitro and in vivo by mitochondrial dysfunction associated apoptosis

Shi, Huaikai and Zhang, Le and Yu, Ta-Kun and Zhuang, Ling and Ke, Helen and Johnson, Ben and Rath, Emma and Lee, Kenneth and Klebe, Sonja and Kao, Steven and Qin, Karl Lijun and Pham, Hong Ngoc Thuy and Vuong, Quan and Cheng, Yuen Yee (2023) Leptospermum extract (QV0) suppresses pleural mesothelioma tumor growth in vitro and in vivo by mitochondrial dysfunction associated apoptosis. Frontiers in Oncology, 13. ISSN 2234-943X

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Link to published document: http://doi.org/10.3389/fonc.2023.1162027


Pleural mesothelioma (PM) is a highly aggressive, fast-growing asbestos-induced cancer with limited effective treatments. There has been interest in using naturally occurring anticancer agents derived from plant materials for the treatment of PM. However, it is unclear if an aqueous extract from Leptospermum polygalifolium (QV0) has activity against PM. Here we investigated the anti-cancer properties of QV0 and Defender((R)) (QV0 dietary formula) in vitro and in vivo, respectively. QV0 suppressed the growth of eight PM cell lines in a dose-dependent manner, effective at concentrations as low as 0.02% w/v (equivalent to 0.2 mg/ml). This response was found to be associated with inhibited cell migration, proliferation, and colony formation but without evident cell cycle alteration. We observed mitochondrial dysfunction post-QV0 treatment, as evidenced by significantly decreased basal and maximal oxygen consumption rates. Ten SCID mice were treated with 0.25 mg/g Defender((R)) daily and exhibited reduced tumor size over 30 days, which was associated with an average extension of seven days of mouse life. There was no evidence of liver toxicity or increased blood glucose post-treatment in animals treated with Defender((R)). Significantly enhanced tumor apoptosis was observed in the Defender((R))-treated animals, correlating to mitochondrial dysfunction. Lastly, the high levels of polyphenols and antioxidant properties of QV0 and Defender((R)) were detected in HPLC analysis. To the best of our knowledge, this study constitutes the first demonstration of an improved host survival (without adverse effects) response in a QV0-treated PM mouse model, associated with evident inhibition of PM cell growth and mitochondrial dysfunction-related enhancement of tumor apoptosis.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 03 Apr 2024 02:51
Last Modified: 03 Apr 2024 02:51
URI: http://eprints.victorchang.edu.au/id/eprint/1445

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