Induction of Apoptosis by Cordyceps militaris through Activation of Caspase-3 in Leukemia HL-60 Cells

Abstract

Apoptosis is characterized by a series of distinct morphological changes including cell shrinkage, membrane bleebing, nuclear breakdown, and DNA fragmentation, and is essential for the maintenance of tissue homeostasis and the elimination of harmful cells.1,2) An apoptotic death stimulus activates caspases, the major executioners of this process, either directly or via the activation of the mitochondrial death program.3,4) The mitochondria-mediated pathway involves an increase of mitochondrial permeability and the release of cytochrome c into the cytosol. 5,6) Cytochrome c promotes the activation of caspase-3 in the cytosol, resulting in the cleavage of an inactive 32 kDa precursor into a 17 kDa and an 11 kDa subunit, which dimerize to form an active enzyme. 7)During the progression of apoptosis, caspase-3 is one of the strongest candidates for the cleavage of 116 kDa native poly (ADP-ribose) polymerase (PARP) into an 86 kDa and a 36 kDa fragment.8) The cleavage of this PARP protein ultimately results in cellular, morphological, and biochemical alterations of apoptosis. 9)Dong-Chong-Xia-Cao in Chinese, which translates as "winter worm and summer grass," is an entomogenous fungus that colonizes the larvae or pupae of insects. It includes many different genera, such as Cordyceps, Paecilomyces, Torrubiella, and Podonectria. The entomopathogenic mycelia naturally grow in the intestine of pupa or larva in the autumn, and fruiting bodies of the fungus protrude from the body in the following summer.10) The fungal fruiting body and the caterpillar host are chemically similar, have similar pharmacological properties, and are traditionally dried and consumed together.Cordyceps sinensis and Cordyceps militaris are representative insect-born fungi of the genus Cordyceps used for medicinal purposes in eastern Asian countries. The known bioactive compounds of these Cordyceps species include cordycepin, 11) ophicordin, 12) a polysaccharide, 13) galactomannan, 14) and L-tryptophan. 15) The recent scientific evaluation of Cordyceps sinensis has confirmed the efficacy of this extract in the treatment of cardiovascular and endocrine disorders, 16) in immune enhancement, 17) in hepatic protection, 18) in the inhibition of tumor growth, 19) and in relieving fatigue and stress. 20)Cordyceps militaris, together with Paecilomyces japonica, another entomopathogenic fungi, has been listed as a food additive in Korea since 2000,21) and is often used in different types of tonic drinks sold in Korea due to its folkloric activities, which have not been verified scientifically. Although some recent studies have reported its effectiveness in inhibiting angiogenesis, 22) cancer cell growth, 23,24) and inflammation, 25) scientific evidences of the biological activities of Cordyceps militaris are still very limited compared to other frequently used insect-born fungi of the Cordyceps species, such as Cordyceps sinensis. It was previously reported by these authors that the hot water extracts of Cordyceps militaris of silkworm pupa (CMP) or silkwo...

Production of Insect Toxin Beauvericin from Entomopathogenic Fungi Cordyceps militaris by Heterologous Expression of Global Regulator

“…This fungi, also known as north cordyceps, is proved to have activities including anticancer, antibacterial, antifungal, and immunoregulative activities. The extract of these fungi may thus be a potential therapy to combat human leukemia (Lee et al, 2006).…”

20(<i>S</i>)-Ginsenoside Rh2 Induces Apoptosis in Human Leukaemia Reh Cells through Mitochondrial Signaling Pathways

“…Caspase-9 can signal downstream and activate pro-caspase-3 and -7. [19][20][21] In the present study, the effect of 20(S)-GRh2 and ginsenoside Rg3 (GRg3) on Reh cell viability was compared. Moreover, we examined nuclear morphology, mitochondrial membrane potential, and status of mitochondria-associated apoptotic proteins analysis in order to elucidate the mechanism of 20(S)-GRh2-induced apoptosis in human acute leukaemia line-Reh cells.…”

Cordyceps Mushroom: A Potent Anticancer Nutraceutical

“…But AECM did not affect the pro-apoptotic gene bax expression and activity of caspase-9. The hot water extract of C. militaris was also found to induce apoptosis in the human premyelocytic leukemia HL-60 cells and the activation of caspase-3 and the specific proteolytic cleavage of Poly ADP-ribose polymerase (PARP) were detected during the course of apoptosis [41]. In addition to the activation of caspase-3, the AECM-induced apoptosis may relate to the inactivation of Akt (an oncogene) in human breast cancer MDA-MB-231 cells [42].…”