Abstract
Osteosarcoma is the most common malignant bone tumor in both children and dogs. It is an aggressive and metastatic cancer with a poor prognosis for long-term survival. The search for new anti-cancer drugs with fewer side effects has become an essential goal for cancer chemotherapy; in this sense, the bioactive compounds from avocado have proved their efficacy as cytotoxic molecules. The objective of this study was to determine the cytotoxic and antiproliferative effect of a lipid-rich extract (LEAS) from Mexican native avocado seed (Persea americana var. drymifolia) on canine osteosarcoma D-17 cell line. Also, the combined activity with cytostatic drugs was evaluated. LEAS was cytotoxic to D-17 cells in a concentration-dependent manner with an IC50 = 15.5 µg/mL. Besides, LEAS induced caspase-dependent cell apoptosis by the extrinsic and intrinsic pathways. Moreover, LEAS induced a significant loss of mitochondrial membrane potential and increased superoxide anion production and mitochondrial ROS. Also, LEAS induced the arrest of the cell cycle in the G0/G1 phase. Finally, LEAS improved the cytotoxic activity of cisplatin, carboplatin, and in less extension, doxorubicin against the canine osteosarcoma cell line through a synergistic effect. In conclusion, avocado could be a potential source of bioactive molecules in the searching treatments for osteosarcoma.
Highlights
Cancer represents a serious human health worldwide problem; recently data of GLOBOCAN indicate that the number of new cases in 2020 has risen to 19.3 million
The results showed that after 24 h of incubation, D-17 cell viability decreased when cells were treated with Lipid-Rich Extract from Avocado Seed (LEAS) 20 μg/mL (29%) (Figure 1A)
The half-maximal inhibitory concentration at 48 h was calculated as IC50 = 15.5 μg/mL, which was corroborated by flow cytometry (Figure 1C,D); this concentration was used in the rest of the experiments
Summary
Cancer represents a serious human health worldwide problem; recently data of GLOBOCAN indicate that the number of new cases in 2020 has risen to 19.3 million. Despite appropriate surgical and chemotherapeutic protocols only approximately 50% of affected dogs survive the first year, and fewer (~20%) survive more than two years after diagnosis [9]. Research in both canine and human OSA has demonstrated that both species share similar genetic abnormalities [8]. Given the high frequency of OSA in canines, the dog is considered an attractive model to study and learn about the origin of this cancer, as well as to evaluate new drugs or treatments that may have potential use in humans too [3,10,11]
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