Abstract
Moringa oleifera, Tropaeolum tuberosum and Annona cherimola are medicinal plants traditionally used in Ecuador. However, their therapeutic properties are not completely known. We analyzed chromatographically ethanolic extracts of the seeds of M. oleifera, A. cherimola and the tubers of T. tuberosum; all presented a high content of polyphenols. The extract of A. cherimola showed the highest antioxidant activity and M. oleifera had the highest capacity to enhance the activity of detoxifying enzymes such as glutathione S-transferase and quinone oxidoreductase. The antitumor effect of these extracts was evaluated in vitro with colorectal cancer (CRC) cell lines T84, HCT-15, SW480 and HT-29, as well as with cancer stem cells (CSCs). A. cherimola and M. oleifera extracts presented the lowest IC50 in T-84 and HCT-15 (resistant) cells, respectively, as well as the highest level of inhibition of proliferation in multicellular tumor spheroids of HCT-15 cells. The inhibitory effect on CSCs is noteworthy because in vivo, these cells are often responsible for cancer recurrences and resistance to chemotherapy. Moreover, all extracts showed a synergistic activity with 5-Fu. The antiproliferative mechanism of the extracts was related to overexpression of caspases 9, 8 and 3 and increased production of reactive oxygen species. In addition, we observed cell death by autophagy in M. oleifera and T. tuberosum extracts. Therefore, these ethanolic extracts are excellent candidates for future molecular analysis of the presence of bioactive compounds and in vivo studies which could improve colon cancer therapy.
Highlights
After breast and lung cancer, colorectal cancer (CRC) is the third most common tumor type worldwide, with 1.9 million new cases diag nosed in 2020, representing 10% of all neoplasms
We identified acetogenins, a class of polyketides belonging to the Annonaceae family, in the A. cherimola ethanolic extract
Our results showed that combining T. tuberosum extract either at 15 μg/mL or 40 μg/mL with 5-FU significantly inhibited the prolif eration of HCT-15 CRC cells (50%) and their multicellular tumor spheroids (MTS) (40%)
Summary
After breast and lung cancer, colorectal cancer (CRC) is the third most common tumor type worldwide, with 1.9 million new cases diag nosed in 2020, representing 10% of all neoplasms. The etiology of CRC involves multiple factors, including a history of colon polyps, inflammatory bowel diseases, diabetes mellitus, the gut microbiome, and lifestyle factors such as inappropriate dietary patterns, obesity, physical inactivity, and tobacco and alcohol use, among others [2]. As a result of these factors, cells at the base of colon crypts form polyps that progress to adenomas and eventually become cancerous [3]. Even though surgical treatment in non-metastatic CRC patients shows acceptable results, chemotherapy is still required in metastatic cases. The severe side effects and low and non-selective antitumor effi cacy of the latter are associated with a poor patient prognosis
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