Cytotoxic Mechanism of Long‐chain Lipids Extracted from Mexican Native Avocado Seed (Persea americana var. drymifolia) on Colon Cancer Cells

Abstract

Cancer represents a worldwide problem, in 2012 about 8.2 million deaths were reported. Colorectal cancer (CRC) is the third most common type of cancer and the fourth leading cause of death in the world, accounting for about 700,000 deaths a year. Chemotherapy currently used in patients with CRC is associated with severe side effects. The use of natural compound combinations extends the possibilities of therapeutic targets. Long chain lipid molecules, such as long chain fatty acids, aliphatic acetogenins and polyhydroxylated fatty alcohols independently have been shown to have anticancer effects and have been proposed as chemo‐therapeutic adjuvants. The main objective of this work was to determine the cytotoxic effect of an extract rich in long chain lipids from Mexican native avocado seed (Persea americana var. drymifolia) on colon cancer cells. Colon adenocarcinoma cell line Caco‐2 was used and viability was measured by trypan blue exclusion assays. Changes in mitochondrial membrane potential, cytokine expression, intracellular calcium levels, cell cycle analysis and ROS production were determined by flow cytometry. The induction of apoptosis was analyzed by flow cytometry; spectrometry and fatty acid oxidation (FAO) rate determination was made using high resolution respirometry. The results showed that the long chain lipids from avocado seed induced apoptosis and the activation of the caspases 8 and 9, loss of the membrane mitochondrial potential (68%), the inhibition of FAO (45%) and the increase in ROS production (30%); however, the intracellular calcium levels were not modified. In addition, cell cycle arrest in the G1/G0 phase was induced. Also, a modulation in cytokine expression (IL‐6, IL‐8, IL‐10 and IL‐1β) was observed. In conclusion, long‐chain lipids from Mexican native avocado seed are cytotoxic towards Caco‐2 cells, inhibiting the FAO which increases ROS production and thus favoring the loss of membrane mitochondrial potential that allows the induction of caspase‐dependent apoptosis. In addition, these molecules induce arrest of the cell cycle and the modulation of cytokines related to the inflammatory response.Support or Funding InformationCIC‐UMSNH 14.5This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.