Mitochondrial dysfunction of halimane and labdane diterpenes in human lung cancer cells

Mitochondrial dysfunctions have been associated with several malfunctions such as increase of ROS and uncontrolled M. tuberculosis (Mtb) replication (1,2) . The electrochemical gradient produced by mitochondria generates the mitochondrial membrane potential (MMP), which is a key parameter for evaluating mitochondrial function (2) . Since the coexistence of tuberculosis and lung cancer has remained controversial, one halimane (HAL: (11 R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid) and two labdane diterpenes PLEC: Plectrornatine C and the MRC: 1:1 mixture of 1,6-di-O-acetylforskolin:1,6-di-O-acetyl-9-deoxyforskolin), previously isolated from Plectranthus spp., (3) were evaluated for the mechanisms of cell death associated with mitochondrial dysfunction. The ROS level and evaluation of the MMP revealed that only HAL decreased mitochondrial membrane potential. In conclusion, the halimane diterpene (HAL) seems to particularly have a cytotoxic effect associated with mitochondrial dysfunction on lung cancer cells that may be further evaluated on the uncontrolled Mtb replication mechanism.