Jasmonic Acid and its Methyl Derivatives: Role in Inhibition of Cancer Cell Cycle Progression as Potential Anti-Cancer Therapeutic Agents

Jaanvi Bhakri, Jhalak Saxena, Pardeep Kumar, Machiavelli Singh*

Amity Institute of Biotechnology, Amity University Haryana, Manesar, 

Gurugram 122413, Haryana, India.

*Corresponding author email: msingh2@ggn.amity.edu

Abstract

Jasmonic acid (JA) and its derivatives are crucial for plant defense and development, serving as signaling molecules in response to various stressors. Recent research has highlighted their involvement in stamen development, senescence, root growth, and the production of secondary metabolites. Methyl jasmonate (MJ), a JA derivative, shows promise as an anti-cancer agent by inhibiting cell cycle progression in cancer cells. MJ has been found to arrest the G1 phase in leukemia and breast cancer cell lines and disrupt the transition to the G2 to M phase in neuroblastoma cells. This effect is associated with the downregulation of the SH-SY5Y gene and the pivotal regulator Myc, which controls genes responsible for cell proliferation and viability. The cytotoxic effect of MJ on lymphomas indicates its ability to induce apoptotic cell death, particularly in cells expressing the wild-type p53 variant. However, different cancer cell types exhibit variable responses to MJ, suggesting diverse mechanisms of action that may involve severe bioenergetic disturbances, such as increased production of Reactive Oxygen Species (ROS), inhibition of ATP synthesis, and anti-inflammatory, anti-angiogenic, and anti-metastatic activities, including the targeting of the 5-lipoxygenase (5-LOX) enzyme. Further research is needed to fully understand the mechanisms underlying the diverse responses of MJ in different cancer cell types.

Keywords: Jasmonic acid, methyl ester (MeJA), isoleucine conjugate (JA-Ile), Jasminum grandiflorum L, mitogen-activated protein kinase (MPK4).