Abstract
BackgroundA 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.MethodsCurcumin-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.ResultsCurcumin-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.ConclusionsCurcumin-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.
Highlights
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
Curcumin and Bioperine (CBP) determines growth inhibition in mesothelioma cells We have previously reported that curcumin (20 μM) only when complexed with cyclodextrin can entry into cells determining cell viability decrease in mesothelioma cells [21]
Wound-healing assay showed that CBP significantly inhibited cell. These results indicated that CBP strongly reduces tumorigenic properties of MM cells, probably by affecting molecular pathways not involved in the response to the combined treatment with piroxicam and cisplatin since the effects are evident even in cells does not responding to this treatment [20]
Summary
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. This treatment determined a marked tumor growth inhibition and an extended survival both in mouse models [3] and in spontaneous MM in pets [4]. Despite the efficacy of this treatment, drug toxicity and tumor-resistance represent a serious limitation. For this reason, research is needed on novel therapeutic approaches using natural compounds with no or little cytotoxicity. Research is needed on novel therapeutic approaches using natural compounds with no or little cytotoxicity In this perspective, phytochemicals represent good candidates to be used alone or associated with standard chemotherapy. Phytochemicals are bioactive plant compounds that display an adjuvant effect resulting in tumor growth inhibition and in chemoprotective action towards the healthy cells with no obvious associated side effects [5]
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