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

Our plain-English summary of Leptospermum extract (QV0) suppresses pleural mesothelioma tumor growth in vitro and in vivo by mitochondrial dysfunction associated apoptosis, by H. Shi, L. Zhang, T.K. Yu, et al (Frontiers in Oncology, 2023).

The study

• Authors: H. Shi, L. Zhang, T.K. Yu, L. Zhuang, H. Ke, B. Johnson, E. Rath, K. Lee, S. Klebe, S. Kao, K.L. Qin, H.N.T. Pham, Q. Vuong, Y.Y. Cheng
• Journal: Frontiers in Oncology
• Published: 2023;13:1162027
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright © 2023 Shi, Zhang, Yu, Zhuang, Ke, Johnson, Rath, Lee, Klebe, Kao, Qin, Pham, Vuong and Cheng.

In plain English

This laboratory and mouse study did not involve people or asbestos exposure. The authors tested QV0, a water extract of Leptospermum polygalifolium leaves and small stems, on pleural mesothelioma cells. QV0 slowed the growth of all eight mesothelioma cell lines tested. The concentration leaving half the cells viable was 0.079 to 0.208 mg/ml for these lines, versus 1.234 mg/ml for a non-cancer mesothelial line. In H2452 and MM05, treated cells moved less and formed fewer colonies, with no evident cell-cycle change; in MSTO, the only cancer line tested for this, mitochondrial oxygen use fell. Mice carrying human mesothelioma cells were given Defender, a honey-based supplement containing 5% QV0, by mouth daily for 30 days. At day 16, treated mice had about 3.16e07 tumor cells, against about 7.67e07 in untreated mice. Their tumors had more dead tissue, and they lived on average 7 days longer. Liver tests and blood glucose did not change. The authors concluded that QV0 inhibits mesothelioma cell growth and improves survival in a mouse model. The products came from a company whose owner is a co-author.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (cell culture) experiments and an animal experiment in mice, with chemical analysis of the extract
• Who was studied: Eight mesothelioma cell lines and one immortalized non-cancer mesothelial cell line (MeT5A).
• The mesothelioma lines were H28, H226, H2452, MSTO, REN, MM05, VMC40 and the mouse line AC29.
• The mice were twenty female SCID mice, 8 weeks old. They were injected in the abdomen with human mesothelioma cells (MSTO-211H) and split into a control group and a Defender group (N = 10 per group).
• The study was run in Sydney, Australia.
• Exposure: Two products were tested:
• QV0, an aqueous extract of L. polygalifolium leaves and small stems, applied to cells.
• Defender (5% QV0, 15% citrus pomace powder, 80% honey), given to mice by oral gavage at 5 mg per 20 g body weight (0.25 mg/g) daily for 30 days.
  No asbestos exposure was studied.
• Main results:
  • The non-cancer MeT5A cell line was more resistant to QV0 (IC50 1.2 ± 0.06 mg/ml) than any of the mesothelioma cell lines. The mesothelioma lines had a mean IC50 of 0.1 ± 0.05 mg/ml, with table values from 0.079 to 0.208 mg/ml.
  • QV0-treated mesothelioma cells migrated a shorter distance in 24 hours (p = 0.003). They also formed fewer colonies. Representative data shown are for cell lines H2452 and MM05.
  • QV0 treatment for 48 hours did not change cell cycle phases in the cancer cells. Cell cycle profiles shown are for H2452 and MM05.
  • Mitochondrial function was measured in one mesothelioma line (MSTO) and in MeT5A.
• In MSTO cells, QV0 lowered basal, maximal and ATP-linked mitochondrial oxygen consumption.
• In the non-cancer MeT5A cells, it had minimal effect on mitochondrial function.
  • At day 16, untreated control mice had approximately 7.67e07 tumor cells and Defender-treated mice approx. 3.16e07 cells. The authors describe this as a 41% inhibition of tumor growth.
  • Dead cells made up approximately 23.94% of tumor tissue in Defender-treated mice, compared with 10.81% in untreated control mice. TUNEL staining showed more apoptotic cells in treated tumors.
  • Defender-treated tumor-bearing mice survived on average 7 days longer than untreated control mice.
  • In treated mice, serum ALT, AST and glucose were not changed after 30 days of Defender. Liver histology showed no signs of liver toxicity.
  • Total phenolic content was 187.9 ± 40.7 mgGAE/g in QV0 and 462.45 ± 59.61 mgGAE/g in Defender. Antioxidant power (FRAP) was 320.7 ± 58.7 mgTE/g in QV0 and 156.25 ± 12.02 mgTE/g in Defender.
• The authors' conclusion: The authors concluded that QV0 inhibits pleural mesothelioma tumor cell growth and improves host survival in a mouse model. They considered this a basis for early-stage clinical trials.
• Limitations the authors state:
  • Most of the more than 30 major compounds detected in the extract have not been identified or tested for anti-cancer properties.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Apoptosis.

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