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DEHP mediates drug resistance by metabolic reprogramming in colorectal cancer cells

Environmental Science and Pollution Research 2023 8 citations ? Citation count from OpenAlex, updated daily. May differ slightly from the publisher's own count.
Yue Wu, Ruijie Lu, Yujie Lin, Jinjin Wang, Zijian Lou, Xiaochun Zheng, Ling Zhang, Ruolang Pan, Gang Lü, Qingxia Fang

Summary

Researchers found that the common plasticizer DEHP triggers metabolic reprogramming in colorectal cancer cells, shifting them from glycolysis to oxidative phosphorylation, which promotes tumor growth and decreases sensitivity to the chemotherapy drug fluorouracil.

Body Systems
Endocrine
Models
Mouse
Study Type In vivo

Long-term exposure to diethylhexyl phthalate (DEHP), an endocrine-disrupting chemical (EDCs) and plasticizer widely used in consumer products, has been reported to be significantly positively correlated with increased risks of different human diseases, including various cancers, while the potential effect of DEHP on colorectal cancer progression was little studied. In the present study, we showed that DEHP could trigger the metabolic reprogramming of colorectal cancer cells, promote cell growth and decrease fluorouracil (5-FU) sensitivity. Mechanistic studies indicated that DEHP could reduce glycolysis activity and increase oxidative phosphorylation (OXPHOS) in SW620 cells. In addition, in vivo experiments showed that DEHP promoted tumorigenic progression and decreased survival time in mice. Collectively, our findings suggest that DEHP may be a potent risk factor for colorectal cancer development.

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