Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 130, Issue -, Pages 1-11Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2019.04.054
Keywords
Non-small cell lung cancer; Cudrania tricuspidata; Kras mutation; Final-2; Autophagy
Categories
Funding
- Guangdong Key Area Research and Development Program [2019B020210003]
- National Natural Science Foundation of China (NSFC) [31871816, 31771978]
- Science and Technology Program of Guangzhou [201704020050]
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Natural products derived from fruits have multiple antitumor potential. However, very few have been developed for clinical therapy, due to the limited efficiency or insufficient study of their mechanism. Since lung cancer is the most common cancer in the world, there is still need to explore novel compounds but their molecular mechanisms remain elusive. In this study, a new compound Final-2 was synthesized. Final-2 exhibited antitumor activity in A549 cells by promoting apoptosis and blocking autophagy. Moreover, Final-2 significantly induced G(0)/G(1) cycle arrest and inhibited cell malignancy. Intracellular molecular targets investigation showed that Final-2 inhibited the Gluts, which resulted in downregulation of glucose metabolism and the oncogene c-Myc and Kras expression in vitro. However, according the autophagy inhibitor CQ and Kras inhibitors test, low concentration of Final-2 showed some controversial effects. In A549 xenograft mice model, 10 mg/kg and 20 mg/kg of Final-2 showed no and partial tumor inhibition, respectively. Moreover, a high dose of Final-2 induced serious liver necrosis. Therefore, the results indicated that even though Final-2 was efficient in suppressing the cancer cell growth in vitro, it failed to inhibit tumors in vivo and showed significant liver toxicity, which was its limitation as a potential antitumor drug.
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