Gal‐3 does not suppress cisplatin‐induced apoptosis in A‐375 melanoma cells

Abstract

Melanoma is the most aggressive of all skin cancers and is exceptionally resistant to therapies. During melanoma progression, cancer cells reprogram their proliferation and survival pathways and achieve resistance to treatment-induced apoptosis. Galectin-3 (gal-3) is a member of the lectin family and is involved in such biological processes as cell adhesion, growth and differentiation, the cell cycle, and apoptosis. Gal-3 also plays an important role in tumor development and metastasis. The relationship between gal-3 expression and these processes is specific to the tumor type and the stage of cancer progression. The biological functions of gal-3 depend on its localization in the cell. In the present study, human metastatic melanoma A-375 cells, characterized by weak endogenous expression of gal-3, were transfected with gal-3 cDNA and cisplatin-induced apoptosis was measured. Data from AnnexinV and mitochondrial membrane potential analysis revealed that gal-3 did not protect the A-375 melanoma cells against cisplatin. This result probably is associated with its nuclear localization in the cells.

MiR-424-3p suppresses galectin-3 expression and sensitizes ovarian cancer cells to cisplatin

“…Among these molecules are miRNAs (small, non-coding RNA molecules of 20–22 nucleotides in length), which are capable to regulate gene expression and are involved in ovarian cancer tumorigenesis [1, 2]. An interesting potential target for miRNAs could be galectin-3, since it is an anti-apoptotic protein that is overexpressed in various tumor cells (including ovarian cancer) and involved in their chemoresistance [3, 5, 7]. Moreover, it has been proved that miR-424-3p (previously also known as miR-322) can modulate galectin-3 expression by decreasing its level [12].…”

“…Galectin-3, a β-galactoside binding lectin, is a well-known suppressor of apoptosis. Chemotherapeutic agents, such as cisplatin, cause the phosphorylation and relocation of the protein from the nucleus to the cytoplasm, where it stabilizes BCL-2, thus blocks cytochrome c release, and inhibits apoptosis [7, 11]. The key element of galectin-3 structure, allowing to suppress apoptosis, is an NWGR (Asp–Trp–Gly–Arg) anti-death motif inside BH1 domain, which galectin-3 shares with the BCL-2 family of proteins [5].…”

“…The C-terminal domain also includes the NWGR (Asp–Trp–Gly–Arg) anti-death motif, which is a part of highly conserved BH1 domain specific to the BCL-2 protein family. The BH1 domain is critical for an anti-apoptotic activity of BCL-2 and also allows cytoplasmic galectin-3 to function as an anti-apoptotic molecule [6, 7]. The NWGR anti-death motif suppresses apoptosis of cancer cells induced by chemotherapeutic agents, such as cisplatin, and thus, galectin-3 plays an important role in the resistance to anticancer drugs [6, 8].…”

“…Increasing evidence suggests that galectin-3 promotes chemoresistance in prostate cancer, cholangiocarcinoma, thyroid carcinoma [9], lung cancer [5], and ovarian cancer [3, 5] as well as protects BT549 human breast carcinoma cells from apoptosis induced by cisplatin, anthracycline, adriamycin, and 5-FU (5-fluorouracil) [5]. Moreover, overexpression of galectin-3 has been reported in multiple types of human tumors, including: ovarian cancer [7]; pancreatic cancer [5, 6, 10, 11]; breast cancer [5, 10, 11]; thyroid, gastric and colon cancer [5, 7, 11]; hepatocellular, head and neck, prostate cancer, and glioma [10]; T lymphoma, Burkitt lymphoma, and cervical cancer [11]. Furthermore, despite contribution in drug resistance, galectin-3 also exhibits pleiotropic biological functions, and is also involved in various pathological cellular processes, such as malignant: transformation, adhesion, angiogenesis, migration, and metastasis [6, 10].…”

Morin decreases galectin-3 expression and sensitizes ovarian cancer cells to cisplatin

“…Galectin-3 in cytoplasm is a well-known anti-apoptotic agent [17]. It contains the NWGR (N, asparagine; W, tryptophan; G, glycine; R, arginine) anti-death motif, which is specific for the BCL-2 family and is resposible for an anti-apoptotic activity of galectin-3 and BCL-2 [16, 18].…”