Diarylbutane-type Lignans from Myristica fragrans (Nutmeg) show the Cytotoxicity against Breast Cancer Cells through Activation of AMP-activated Protein Kinase

In our program to search for new AMP-activated protein kinase (AMPK) activators from plants that exert potential anticancer property, we found that an EtOAc extract of Myristica fragrans (nutmeg) activated AMPK enzyme in human breast cancer MCF-7 cells. Two major diarylbutane-type lignans, macelignan and meso-dihydroguaiaretic acid (MDGA), were isolated as active principles from this extract. Treatment of breast cancer cells with two compounds induced cellular apoptosis, evidenced by cleavage of poly-(ADP-ribose) polymerase (PARP) and Ser 15 phosphorylation of p53. Moreover, macelignan and MDGA significantly inhibited the colony formation of MCF-7 breast cancer cells on soft agar. Intraperitoneal injection of macelignan and MDGA (20 mg/kg) suppressed the tumor growth of 4T1 mammary cancer cells. These results indicate that the chemopreventive effects of two major diarylbutane-type lignans from Myristica fragrans (nutmeg) may be associated with induction of apoptosis presumably through AMPK activation.

An Unusual Odontogenic Cyst with Diverse Histologic Features

An unusual odontogenic cyst, which was originally believed to be a clinical dentigerous cyst associated with an impacted mandibular third molar, was found histologically to demonstrate the characteristics of a glandular odontogenic cyst with para- and orthokeratinization. These histologic diversities were interpreted as a reflection of the pluripotentiality of the epithelial remnants of the mandibular third molars or dentigerous cyst epithelium. It is possible that it has the capacity to induce the formation of cysts in both squamous and glandular epithelium.

Comparison of new bone forming activity after osteotomy using Er:YAG laser and conventional bur in rabbit mandible

Myoepithelioma of the hard palate

A comparative Ki-67 expression of odontogenic keratocysts(OKCs) with or without impacted tooth

Clinical and histopathologic analysis of traumatic bone cysts of the jaws

Comparative Ki-67 Expression and Apoptosis in the Odontogenic Keratocyst Associated with or without an Impacted Tooth in Addition to Unilocular and Multilocular Varieties

It is not known whether the presence of an impacted tooth or the radiographic types in an odontogenic keratocyst (OKC) change the clinical biologic behavior and therapeutic approaches. This study evaluated the comparative proliferative activity and apoptosis in OKC associated with or without an impacted tooth, as well as between the unilocular and multilocular OKC varieties. Immunohistochemical expression of Ki-67 as a proliferation marker and the apoptotic reactions were assessed by the TUNEL method for 32 cases of OKC (OKC with impacted tooth, n=16; OKC without impacted tooth, n=16) and 10 cases of dentigerous cyst (DC). OKC showed a greater proliferative potential and more apoptotic reactions than DC. In particular, OKC contained proliferating and apoptotic cells situated predominantly in the suprabasal and superficial layers, respectively. However, no significant difference was found between OKC associated with or without impacted tooth, or between the unilocular and multilocular OKC varieties, in terms of proliferative activity or apoptosis. In conclusion, OKC is characterized by an increase in both cell proliferation and apoptosis, suggesting a unique proliferative and differentiation process. It is believed that incomplete removal or other contributing factors, rather than intrinsic growth or apoptosis, may be the main reasons for the aggressive biologic behavior or recurrence in multilocular OKC.

Sox-4 is a positive regulator of Hep3B and HepG2 cells' apoptosis induced by prostaglandin (PG)A2 and 12-PGJ2

We reported earlier that expression of Sox-4 was found to be elevated during prostaglandin (PG) A2 and delta(12)-PGJ(12) induced apoptosis in human hepatocarcinoma Hep3B cells. In this study, the role of Sox-4 was examined using human Hep3B and HepG2 cell lines. Sox-4 induction by several apoptotic inducer such as A23187 (Ca(2+) ionophore) and etoposide (topoisomerase II inhibitor) and Sox-4 transfection into the cells were able to induce apoptosis as observed by the cellular DNA fragmentation. Antisense oligonucleotide of Sox-4 inhibited the induction of Sox-4 expression and blocked the formation of DNA fragmentation by PGA(2) and delta(12)-PGJ(12) in Hep3B and HepG2 cells. Sox-4-induced apoptosis was accompanied with caspase-1 activation indicating that caspase cascade was involved in this apoptotic pathway. These results indicate that Sox-4 is involved in Hep3B and HepG2 cells apoptosis as an important apoptotic mediator.

Active adenosine transporter-mediated adenosine entrance into HL-60 cells leads to the induction of apoptosis through down-regulation of c-Myc

Although adenosine (Ado) is being recently recognized as a potent inducer of apoptosis, molecular mechanism of apoptosis by Ado remains to be elucidated. In this study we observed that c-Myc was rapidly down-regulated in the apoptosis in human promyelocytic leukemia HL-60 cells treated with Ado. To establish the molecular and biochemical mechanisms of apoptosis, we tested the specific effects of several antagonists of Ado receptors or inhibitors of Ado transporter on the induction of apoptosis. Treatment of dipyridamole (DPD), an Ado transport inhibitor, effectively suppressed both c-Myc reduction and DNA fragmentation, suggesting that the induction of apoptosis and down-regulation of c-Myc is mediated by active Ado transporter. It was another evidence supporting the entrance of Ado into cells undergoing apoptosis that Ado cytotoxicity was potentiated by a addition of methylation cycle intermediates. These results suggest that the active Ado transporter-mediated Ado entrance into HL-60 cells leads to the induction of apoptosis through down-regulation of c-Myc.