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Effect of suramin on squamous differentiation and apoptosis in three human non‐small cell lung cancer cell lines
Author(s) -
Lokshin Anna,
Levitt Mark L.
Publication year - 1996
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240630514
Subject(s) - suramin , apoptosis , cancer research , biology , lung cancer , cell culture , cell growth , cancer cell , cancer , immunology , medicine , receptor , biochemistry , genetics
Abstract Non‐small cell lung cancer (NSCLC) is fatal in approximately 90% of all cases due to the failure of systemic therapy, secondary to resistance to chemotherapy. In such malignancies new therapeutic paradigms are needed. One such approach takes advantage of normal physiologic growth regulatory mechanisms, such as terminal cellular differentiation or apoptosis. Suramin, as an antineoplastic drug, has shown efficacy in the treatment of prostate cancer and is capable of promoting differentiation in several human cancer cell lines. Little is known about the differentiating effects of suramin in lung cancer. In the present investigation we evaluated the ability of suramin to induce cross‐linked envelope (CLE) formation, as a common marker for squamous differentiation and apoptosis, in three representative human non‐small cell lung cancer cell lines: NCI‐H226 (squamous), NCI‐H358 (bronchoalveolar [adenocarcinoma]), and NCI‐H596 (adenosquamous). Among agents that we have tested, suramin demonstrated the unique ability to induce spontaneous CLE formation in the two cell lines with squamous features, NCI‐H226 and NCI‐H596. Suramin induced CLE formation was accompanied by DNA fragmentation, a marker for apoptosis, in NCI‐H596 and NCI‐H358, but not in NCI‐H226. Stimulation of CLE formation by suramin correlated with the rapid induction of both type II transglutaminase (TG) activity and involucrin expression. These parameters were protein synthesis independent, suggesting posttranslational mechanisms of suramin activity. Induction of differentiation/apoptosis markers by suramin did not correlate with its effect on growth. Modulation of signal transduction is a likely candidate mechanism for suramin activity in lung cancer. The relationship between growth, squamous differentiation, and apoptosis is considered. © 1996 Wiley‐Liss, Inc.