Background: Cancer metabolism is a new and exciting field of biology that provides a fundamentally different approach to treating cancer. The characteristic of cancer metabolism is Warburg effect formation that is the glucose metabolism in the glycolytic pathway in aerobic environments. Specific high expression of PKM2 (Pyruvate kinase type M2) is indispensable to the Warburg effect formation. Curcumin is an ingredient of Termeric, and has a variety of bioactivity with less toxicity. Recently, an anti-cancer effect of Curcumin attracts attention, and various studies are conducted to investigate the bio-mechanisms as an anti-cancer agent. While Curcumin has been reported to provide an anti-cancer effect by suppressing NF-κB-COX pathway and/or the oxidative stress, its effect on cancer metabolism still remains unclear. Here, we investigated the mechanism of anti-cancer effects derived by Curcumin by focusing on cancer metabolism.
Method: The anti-cancer effect of Curcumin was examined by growth-assay in HCC cell lines (HepG2 and HLF). To further assess the biological mechanism of Curcumin on cancer cells, the changes in cancer metabolic pathways such as pyruvate kinase type M2 (PKM2), glucose transporter1 (Glut1), glucose-6-phosphate dehydrogenase deficiency (G6PD), and Transketolase (TKT).
Result: In growth assay, Curcumin treatment significantly suppressed cell growth of HepG2 cell. For the cancer metabolic pathways, Curcumin treatment induced a shift into PKM1 from PKM2 expression represented by decreased PKM2/1 ratio by real time PCR in HepG2 and HLF cells. Indeed, Glut1 and G6PD expressions were also suppressed by Curcumin treatment, whereas TKT expression was increased in HepG2 cell.
Conclusion: Curcumin displayed anti-proliferative effects on HCC cell lines, and its anti-cancer effects may be due to normalize the cancer metabolic pathway represented by a shift into PKM1 from PKM2 expression.
Citation Format: Hideaki Takeyama, Hiromitsu Hayashi, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Takaaki Higashi, Hirohisa Okabe, Hidetoshi Nitta, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba. Curcumin may have anticancer effect by normalizing cancer metabolic pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1175. doi:10.1158/1538-7445.AM2015-1175