Curcumin C3 complex®/Bioperine® has antineoplastic activity in mesothelioma: an in vitro and in vivo analysis

Our plain-English summary of Curcumin C3 complex®/Bioperine® has antineoplastic activity in mesothelioma: an in vitro and in vivo analysis, by F. Di Meo, S. Filosa, M. Madonna, et al (Journal of Experimental & Clinical Cancer Research, 2019).

The study

• Authors: F. Di Meo, S. Filosa, M. Madonna, G. Giello, A. Di Pardo, V. Maglione, A. Baldi, S. Crispi
• Journal: Journal of Experimental & Clinical Cancer Research
• Published: 2019;38(1):360
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: A major limitation in the treatment for malignant mesothelioma is related to serious side effects caused by chemotherapeutics and to the development of cancer-resistance. Advances in cancer therapies have been reached thanks to the introduction of alternative approaches, such as the use of phytochemicals. Curcumin-C3complex®/Bioperine® is a commercially standardized extract containing a ratio-defined mixture of three curcuminoids and piperine that greatly increase its bioavailability. Interestingly, the anticancer effect of this formulation has been described in different studies and several clinical trials have been started, but to our knowledge none refers to human mesothelioma.

Methods: Curcumin-C3complex®/Bioperine® anticancer effect was evaluated in vitro in different human mesothelioma cell lines analysing cell proliferation, colony-forming assay, wound healing assays, invasion assay and FACS analysis. In vivo anticancer properties were analysed in a mesothelioma xenograft mouse model in CD1 Nude mice.

Results: Curcumin-C3complex®/Bioperine® in vitro induced growth inhibition in all mesothelioma cell lines analysed in a dose- and time-depended manner and reduced self-renewal cell migration and cell invasive ability. Cell death was due to apoptosis. The analysis of the molecular signalling pathway suggested that intrinsic apoptotic pathway is activated by this treatment. This treatment in vivo delayed the growth of the ectopic tumours in a mesothelioma xenograft mouse model.

Conclusions: Curcumin-C3complex®/Bioperine® treatment strongly reduces in vitro tumorigenic properties of mesothelioma cells by impairing cellular self-renewal ability, proliferative cell rate and cell migration and delays tumor growth in xenograft mouse model by reducing angiogenesis and increasing apoptosis. Considering that curcumin in vivo synergizes drug effects, its administration to treatment regimen may help to enhance drug therapeutic efficacy in mesothelioma. Our results suggest that implementation of standard pharmacological therapies with novel compounds may pave the way to develop alternative approaches to mesothelioma.

In plain English

This was a laboratory study. It did not study people or asbestos exposure. The authors tested a commercial curcumin extract (Curcumin C3 complex) combined with piperine (Bioperine), which they called CBP. They tested it on three human malignant mesothelioma cell lines (MSTO, NCI-H2452 and Ist-Mes-2) and on nude mice carrying tumours grown from injected human mesothelioma cells. In the cell lines, CBP at 20 μM almost completely blocked colony formation and reduced cell invasion and migration. It also caused programmed cell death (apoptosis) that reached about 75% at 72 hours, and it worked in Ist-Mes-2 cells too. In mice (8 per group), daily CBP injections for 4 weeks significantly delayed tumour growth compared with controls, but less effectively than cisplatin. Tumours in CBP-treated mice had fewer dividing cells (10% versus 25% in controls), more dying cells (8% versus 2%) and fewer blood vessels. The authors stated that CBP did not control bulky tumours. They called for further studies before clinical trials.

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 study: experiments on human mesothelioma cell lines (in vitro) and an animal experiment in a mouse xenograft model (in vivo)
• Who was studied: Three human malignant mesothelioma cell lines (MSTO-221H, NCI-H2452, Ist-Mes-2), and male CD1 Nude mice injected under the skin with human mesothelioma cells (MSTO-211H). 8 mice per group were randomly assigned to control (DMSO), CBP or cisplatin.
• Exposure: No asbestos exposure was studied. The treatment tested was CBP (Curcumin C3 complex plus Bioperine, 100:1 by weight). The cells received 20 μM for most experiments. The mice received 40 mg/kg CBP by intraperitoneal injection daily for 4 weeks. Comparison groups were cisplatin (3.3 mg/kg for the first 3 days) and vehicle (DMSO) controls.
• Main results:
  • In all three mesothelioma cell lines, colony formation was almost completely inhibited after 24-hour CBP treatment.
  • In the treated cell lines, CBP caused apoptosis that increased over time, reaching about 75% at 72 hours. No apoptotic increase was seen in untreated cells.
  • CBP was also effective in Ist-Mes-2 cells, which the authors note do not undergo apoptosis after piroxicam and cisplatin treatment.
  • Molecular analyses in the cell lines indicated that CBP activated the intrinsic apoptotic pathway.
  • In the mouse xenograft model, CBP significantly delayed tumour growth compared with controls (p = 0.0013), but with lower efficacy than cisplatin (p = 0.0011).
  • In mouse tumours, CBP treatment versus control was associated with the following: cell proliferation (Ki-67) 10% in treated vs 25% in controls (p = 0.008); apoptosis (TUNEL) 8% in treated vs 2% in controls (p = 0.0005); vessel count 5 ± 2 in treated vs 10 ± 4 in controls (p = 0.0006).
• The authors' conclusion: The authors concluded that CBP showed previously unappreciated anti-cancer effects in a model of malignant mesothelioma. They said further studies on the exact molecular mechanisms are required before future randomized clinical trials of CBP in mesothelioma.
• Limitations the authors state:
  • The authors stated that under their experimental conditions CBP was ineffective in controlling bulky tumours.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Clinical Trial, Apoptosis, Angiogenesis.

Related studies

• Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis — Y. Wang, A.K. Rishi, et al. (2011)
• Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma — C. Zhang, Y. Hao, et al. (2018)
• Antitumor activity of MEK and PI3K inhibitors against malignant pleural mesothelioma cells in vitro and in vivo — S. Miyoshi, H. Hamada, et al. (2012)
• Blockade of aquaporin 1 inhibits proliferation, motility, and metastatic potential of mesothelioma in vitro but not in an in vivo model — S. Klebe, K. Griggs, et al. (2015)
• Curcumin as an Anticancer Agent in Malignant Mesothelioma: A Review — A. Baldi, A. De Luca, et al. (2020)
• In Vitro and In Vivo Antitumor Activity of [Pt(O,O'-acac)(γ-acac)(DMS)] in Malignant Pleural Mesothelioma — A. Muscella, C. Vetrugno, et al. (2016)

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