Abstract
Malignant mesothelioma is an aggressive cancer with limited therapeutic options. Sialic acid-binding lectin isolated from Rana catesbeiana oocytes (cSBL) is a multifunctional protein with anti-cancer activity. The effects of pemetrexed, cisplatin, and cSBL were evaluated in mesothelioma and normal mesothelial cell lines. We evaluated cytotoxicity, apoptosis, caspase-3 cleavage and activation, cell proliferation, cell cycle arrest, and levels of cell cycle proteins in H28 cells treated with pemetrexed, cisplatin, and cSBL alone or in combination. Treatment with cSBL alone was cytotoxic to mesothelioma cells. The anti-cancer effect of cSBL was observed in a broader range of cell lines and exhibited greater cancer cell selectivity than pemetrexed or cisplatin. Combination treatment with pemetrexed + cSBL resulted in greater dose-dependent cytotoxicity than pemetrexed + cisplatin, the standard of care in mesothelioma. The synergistic effect of pemetrexed + cSBL was mediated by the cytostatic effect of pemetrexed and the cytotoxic effect of cSBL. It thus appears that cSBL has therapeutic potential for the treatment of mesothelioma.
Highlights
Malignant mesothelioma is an aggressive cancer of mesothelial cell origin that results from exposure to asbestos [1, 2]
CSBL exhibits greater cancer cell selectivity than pemetrexed and cisplatin We evaluated the effects of cSBL, pemetrexed, and cisplatin on the viability of epithelioid mesothelioma cells (NCI-H2452 [H2452], MESO-1, and MESO-4), biphasic mesothelioma cells MSTO-211H (MSTO) and sarcomatoid mesothelioma cells (H28), and non-malignant mesothelial cells (MeT5A) using WST-8 assays
H2452, MESO-1, and MESO-4 cells were resistant to pemetrexed (RS: 0.37, 0.06, and 0.06, respectively), and H28, H2452, and MESO-1 cells were resistant to cisplatin (RS: 0.66, 0.24, and 0.26, respectively)
Summary
Malignant mesothelioma is an aggressive cancer of mesothelial cell origin that results from exposure to asbestos [1, 2]. Asbestos was extensively used in industry and construction during the 20th century. It was first associated with the incidence of mesothelioma in the 1960s [3,4,5,6]. Because mesothelioma develops 20–30 years after asbestos exposure, the number of mesothelioma patients is expected to increase [7,8,9]. The folate antimetabolite pemetrexed is a chemotherapeutic that is typically used in combination with platinum-containing drugs such as cisplatin [10, 11]. Most patients treated with pemetrexed and cisplatin experience tumor progression or relapse within a year [12, 13].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
