Fisetin modulates mitochondrial enzymes and apoptotic signals in benzo(a)pyrene-induced lung cancer

Abstract

The present study was aimed to delineate in vivo mechanisms of orally administered fisetin with special reference to mitochondrial dysfunction in lung tissues employing benzo(a)pyrene (B(a)P) as the model lung carcinogen. The recent revival of interest in the study of mitochondria has been stimulated by the evidence that genetic and/or metabolic alterations in this organelle lead to a variety of human diseases including cancer. These alterations could be either causative or contributing factors. Hence, the activities of mitochondrial-specific enzymes of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and tumor marker, carcinogenic embryonic antigen were analyzed in control and experimental groups of mice. The induction of apoptotic and anti-apoptotic proteins such as Bcl-2/Bax, cytochrome c, caspase-9 and caspase-3 was confirmed by the immunohistochemistry and Western blot analyses. Furthermore, transmission electron microscopy study of lung sections of B(a)P-induced mice showed the presence of phaemorphic cells with dense granules and increased mitochondria. All the aberrations were alleviated when the mice were treated with fisetin (25 mg/kg body weight). The results proved fisetin to be a very successful drug in combating the mitochondrial dysfunction in an experimental model of lung carcinogenesis induced by B(a)P.

Lagerstroemia Speciosa (L.) Pers Leaf Extract Attenuates Lung Tumorigenesis via Alleviating Oxidative Stress, Inflammation and Apoptosis

“…Numerous studies have implicated imbalance between cell proliferation and apoptosis in many pathological conditions. In fact, apoptosis has a central role in restricting tumor cell expansion, and apoptosis inhibition is pivotal to carcinogenesis [81].…”

Dietary flavonoid fisetin for cancer prevention and treatment

“…Fisetin treatment increased cleavage of caspase‐9 and caspase‐3 thereby increasing caspase‐3 activation . Similarly, fisetin supplementation alleviated mitochondrial dysfunction and induced apoptosis by the upregulation of Bax/Bcl‐2 ratio, thereby leading to cytochrome‐c release and activation of caspase‐9, caspase‐3 leading to apoptotic cell death during benzo(a)pyrene (B(a)P)‐induced lung cancer in‐vivo . Fisetin (25 mg/kg body weight) decreased histological lesions and levels of lipid peroxidation and modulated the enzymatic and nonenzymatic anti‐oxidants in B(a)P‐treated Swiss Albino mice .…”

Exploring the molecular targets of dietary flavonoid fisetin in cancer

“…The effect of fisetin on mitochondrial enzymes with induction of apoptosis was also observed in benzo(a)pyrene-induced lung cancer animal model. Histopathological studies of lung sections of these mice showed the presence of phaemorphic cells with dense granules and increased mitochondria while these aberrations were alleviated in fisetin treated mice [68]. …”