Abstract
Simple SummaryThe recovery rate in patients with metastatic colorectal cancer (CRC) remains low and declines with successive lines of treatment. This phenomenon is caused by the development of drug resistance and the presence of colorectal cancer stem cells (CSCs). Phytochemicals, like -celastrol and resveratrol, are very promising for colon cancer therapy, owing to their low or no toxicity and their pleiotropic activity, enabling them to interact with various biological targets. In the present study, the potential anticancer mechanisms of both compounds against metastatic colon cancer cells and the capacity to eradicate CSCs were investigated.Metastatic colorectal cancer (CRC) remains a hard-to-cure neoplasm worldwide. Its curability declines with successive lines of treatment due to the development of various cancer resistance mechanisms and the presence of colorectal cancer stem cells (CSCs). Celastrol and resveratrol are very promising phytochemicals for colon cancer therapy, owing to their pleiotropic activity that enables them to interact with various biological targets. In the present study, the anticancer activities of both compounds were investigated in metastatic colon cancer cells (LoVo cells) and cancer stem-like cells (LoVo/DX). We showed that celastrol is a very potent anti-tumor compound against metastatic colon cancer, capable of attenuating CSC-like cells at the molecular and cellular levels. In contrast, resveratrol has a much greater effect on colon cancer cells that are expressing standard sensitivity to anticancer drugs, than on CSC-like cells. In addition, both polyphenols have different influences on the expression of SIRT genes, which seems to be at least partly related to their anti-tumor activity.
Highlights
Despite the increasing number of treatment options available over the last years, colorectal cancer (CRC) is still one of the most therapy-resistant solid tumors
Doxorubicin-resistant LoVo/Dx cells were chosen as the in vitro cellular model of aggressive and resistant colon cancer enriched in cancer stem cells (CSCs)
We show that LoVo/Dx cells display significantly higher activities of multidrug resistance (MDR) transporters as detected by the efflux of fluorescent probes used as model MDR-substrates: Rhodamine
Summary
Despite the increasing number of treatment options available over the last years, colorectal cancer (CRC) is still one of the most therapy-resistant solid tumors. Treatment failure and disease relapse in patients with CRC are associated with the presence of intrinsic and/or acquired resistance of cancer cells. Resistance to therapy and cancer recurrence have been attributed to the presence of cancer stem cells (CSCs) within the tumor mass [3]. The CSCs population is associated with either the accumulation of genetic and epigenetic alterations in colorectal stem cells and normal tumor cells, or the dedifferentiation of somatic cells caused by various genetic and environmental factors. Designing a new therapeutic strategy to aid the elimination of CSCs is imperative to improve the treatment of colorectal cancer
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