Journal
CELLULAR & MOLECULAR BIOLOGY LETTERS
Volume 26, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s11658-021-00263-y
Keywords
Worenine; Warburg effect; Colon cancer; HIF-1α Glycolysis
Categories
Funding
- National Natural Science Foundation of China [82074318, 81930117, 81973523]
- National Key R&D Program of China [2017YFC1700602]
- Priority Academic Program Development of Jiangsu Higher Education Institutions: Changshu Health and Family Planning Commission Supporting Project [CSWS201514]
- Suzhou Municipal Science and Technology Bureau Supporting Project [SYSD2016015, SYSD2019004, SYSD2019195]
- Changshu Municipal Science and Technology Bureau Supporting Project [CS201623, CS201808]
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The study found that worenine can affect the glucose metabolism and glycolysis of colorectal cancer cells, with anti-cancer effects and the ability to reverse the Warburg effect. The results suggest that worenine may target HIF-1 alpha to inhibit the growth and proliferation of colorectal cancer cells.
Background Some natural compounds inhibit cancer cell growth in various cancer cell lines with fewer side effects than traditional chemotherapy. Here, we explore the pharmacological effects and mechanisms of worenine (isolated from Coptis chinensis) against colorectal cancer. Methods The effects of worenine on colorectal cancer cell proliferation, colony formation and cell cycle distribution were measured. Glycolysis was investigated by examining glucose uptake and consumption, lactate production, and the activities and expressions of glycolysis enzymes (PFK-L, HK2 and PKM2). HIF-1 alpha was knocked down and stimulated in vitro to investigate the underlying mechanisms. Results Worenine somewhat altered the glucose metabolism and glycolysis (Warburg effect) of cancer cells. Its anti-cancer effects and capability to reverse the Warburg effect were similar to those of HIF-1 alpha siRNA and weakened by deferoxamine (an HIF-1 alpha agonist). Conclusion It is suggested that worenine targets HIF-1 alpha to inhibit colorectal cancer cell growth, proliferation, cell cycle progression and the Warburg effect.
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