Noscapine is an isoqiunoline alkaloid found in opium latex. Unlike most other alkaloids obtained from opium latex, noscapine is not sedative and has been used as antitussive drug in various countries. Recently, it has been introduced as an anti-mitotic agent. This drug can be used orally. When the resistance to other anti-cancer drugs such as paclitaxel manifests, noscapine might be effective. Therefore, noscapine and its analogs have great potential as novel anti-cancer agents.
Atypical glandular cells (AGC) often cause diagnostic uncertainty in cervicovaginal smears. To determine the incidence of significant pathologies associated with AGC on Papanicolaou test, AGC smears were correlated with subsequent biopsy diagnoses. A retrospective review of archives of our cytology files for cervicovaginal smears diagnosed as AGC from April 1998 to March 2001 was performed. In 9390 cervicovaginal smears, AGC were reported in 76 (0.81%) cases, with histologic follow-up in 42 patients (55.3%). Twenty-two patients (52.4%) had preneoplastic or neoplastic, squamous, or glandular lesions on histologic examination. Among them were cervical intraepithelial neoplasia, basal cell abnormality of undetermined significance, cervical adenocarcinoma, endometrial hyperplasia or adenocarcinoma, vaginal adenocarcinoma, endocervical glandular dysplasia, metastatic breast carcinoma, and simple nonvillous trophoblastic tissue. Therefore, presence of AGC in cervical smears may exhibit a spectrum of findings, ranging from benign/reactive changes to squamous or glandular premalignancy or malignancy. A majority of these lesions are squamous dysplasia, and a significant number of patients had glandular malignancy. The results of the current study underline the importance of follow-up for patients with the diagnosis of AGC. To our knowledge, this is the first report in Iran showing the significance of AGC diagnosis.
It has been shown that noscapine, an opium-derived phthalideisoquinoline alkaloid that is currently being used as an oral antitussive drug, induces apoptosis in myeloid leukemia cells. The molecular mechanism responsible for the anticancer effects of noscapine is poorly understood. In the current study, the apoptotic effects of noscapine on two myeloid cell lines, apoptosis-proficient HL60 cells and apoptosis-resistant K562 cells, were analyzed. An increase in the activity of caspase-2, -3, -6, -8 and -9, poly(ADP ribose) polymerase cleavage, detection of phosphatidylserine on the outer layer of the cell membrane, nucleation of chromatin, and DNA fragmentation suggested the induction of apoptosis. Noscapine increased the Bax/Bcl-2 ratio with a significant decrease of Bcl-2 expression accompanied with Bcl-2 phosphorylation. Using an inhibitory approach, the activation of the caspase cascade involved in the noscapine-induced apoptosis was analyzed. We observed no inhibitory effect of the caspase-8 inhibitor on caspase-9 activity. In view of these results and taking into consideration that K562 cells are Fas-null, we suggested that caspase-8 is activated in a Fas-independent manner downstream of caspase-9. In conclusion, noscapine can induce apoptosis in both apoptosis-proficient and apoptosis-resistant leukemic cells, and it can be a novel candidate in the treatment of hematological malignancies.
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