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

Huaikai Shi; Le Zhang; Ta-Kun Yu; Ling Zhuang; Helen Ke; Ben Johnson; Emma Rath; Kenneth Lee; Sonja Klebe; Steven Kao; Karl Lijun Qin; Hong Ngoc Thuy Pham; Quan Vuong; Yuen Yee Cheng

doi:10.3389/fonc.2023.1162027

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

Front Oncol. 2023 Jul 5:13:1162027. doi: 10.3389/fonc.2023.1162027. eCollection 2023.

Authors

Huaikai Shi¹, Le Zhang², Ta-Kun Yu¹, Ling Zhuang¹, Helen Ke¹, Ben Johnson¹, Emma Rath³, Kenneth Lee^{4

5}, Sonja Klebe^{1

6}, Steven Kao^{1

7}, Karl Lijun Qin⁸, Hong Ngoc Thuy Pham^{9

10}, Quan Vuong⁹, Yuen Yee Cheng²

Affiliations

¹ Asbestos and Dust Diseases Research Institute, Sydney, NSW, Australia.
² Institute for Biomedical Materials & Devices (IBMD), Faculty of Science, The University of Technology, Sydney, NSW, Australia.
³ Giannoulatou Laboratory, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia.
⁴ Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
⁵ Pathology, Concord Repatriation General Hospital, Sydney, NSW, Australia.
⁶ Pathology, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, Australia.
⁷ Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, NSW, Australia.
⁸ Quality Global Supply Pty. Ltd., Tuggerah, NSW, Australia.
⁹ College of Engineering, Science and the Environment, University of Newcastle, Sydney, NSW, Australia.
¹⁰ Faculty of Food Technology, Nha Trang University, Nha Trang, Vietnam.

Abstract

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^® (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^® 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^®. Significantly enhanced tumor apoptosis was observed in the Defender^®-treated animals, correlating to mitochondrial dysfunction. Lastly, the high levels of polyphenols and antioxidant properties of QV0 and Defender^® 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.

Keywords: Leptospermum; anti-cancer (anticancer) drugs; apoptosis; mitochondria dysfunction; pleural mesothelioma.