Title:Combined Chemotherapy or Biotherapy with Jasmonates: Targeting Energy Metabolism for Cancer Treatment
Volume: 14
Issue: 3
Author(s): Uri Elia and Eliezer Flescher
Affiliation:
Keywords:
Cancer, chemotherapy, combinational drug therapy, jasmonate, metabolism, mitochondria, calcium homeostasis, Warburg effect
Abstract: Mitochondria are known to play a key role in various cellular processes essential to both the life and death of
cells, including calcium homeostasis, programmed cell death, and energy metabolism. Over 80 years ago, Otto Warburg
discovered that in contrast to normal cells which produce most of their ATP via mitochondrial oxidative phosphorylation,
cancer cells preferentially utilize glycolysis for production of ATP, a phenomenon known today as the "Warburg effect",
and one which has been of great importance in the emergence of novel drugs and chemotherapeutic agents specifically
targeting cancer cells. Several groups have reported in recent years that members of the plant stress hormones family of
jasmonates, and some of their synthetic derivatives, exhibit anti-cancer activity in vitro and in vivo. Jasmonates have been
shown to act directly on mitochondria of cancer cells, leading to mitochondrial swelling, membrane depolarization and cytochrome
c release. Throughout the last few years, different groups have demonstrated that combination of jasmonates and
various cytotoxic and chemotherapeutic agents yielded a synergistic cytotoxic effect. These results have been demonstrated
in a variety of different cancer cell lines and may provide a strong basis for future clinical treatments which involve
combination of MJ and different anti-cancerous agents. The potential synergistic effect may allow reduction of the
administered dose, decrease of unwanted side effects, and reduction of the likelihood that the tumor will display resistance
to the combined therapy.
