Natural substance can block a newly discovered cancer cell energy pathway

Looking to nature for answers to complex questions can reveal new and unprecedented results that can even affect cells on molecular levels.

For instance, human cells oxidize glucose to produce ATP (adenosine triphosphate), an energy source necessary for life. Cancer cells produce ATP through glycolysis, which does not utilize oxygen even under conditions where oxygen is present, and convert glucose into pyruvic acid and lactic acid.

This method of producing ATP, known as the Warburg effect, is considered inefficient, thus raising questions as to why cancer cells choose this energy pathway to fuel their proliferation and survival.

In search of this energy catalyst, Associate Professor Akiko Kojima-Yuasa’s team at Osaka Metropolitan University’s Graduate School of Human Life and Ecology analyzed the cinnamic acid ester ethyl p-methoxycinnamate, a main component of kencur ginger, and its mechanism of action.

In previous research, the team discovered that ethyl p-methoxycinnamate has inhibitory effects on cancer cells. Furthering their study, the acid ester was administered to Ehrlich ascites tumor cells to assess which component of the cancer cells’ energy pathway was being affected.

The new results, published in Scientific Reports, revealed that the acid ester inhibits ATP production by disrupting de novo fatty acid synthesis and lipid metabolism, rather than through glycolysis as commonly theorized. Furthermore, the researchers discovered acid-ester-induced inhibition triggered increased glycolysis, which acted as a possible survival mechanism in the cells. This adaptability was theorized to be attributed to ethyl p-methoxycinnamate’s inability to induce cell death.

“These findings not only provide new insights that supplement and expand the theory of the Warburg effect, which can be considered the starting point of cancer metabolism research, but are also expected to lead to the discovery of new therapeutic targets and the development of new treatment methods,” stated Professor Kojima-Yuasa.