Molecular Mechanism of Cell Apoptosis by Paclitaxel and Pirarubicin in a Human Osteosarcoma Cell Line

Abstract

Background: Paclitaxel and pirarubicin exhibit cytotoxic and antitumor activities. However, little is known about the apoptosis-inducing effects of paclitaxel and pirarubicin on human osteosarcoma MG-63 cells. Methods: The effects of paclitaxel and pirarubicin on cell cycle arrest and apoptosis were studied in MG-63 cells using flow cytometry. PCNA, Bcl-2, Bax, cyclin D1 and cyclin E expression was assessed by Western blotting. Results: Paclitaxel and pirarubicin caused G2/M and G0/G1 cell cycle arrest in MG-63 cells, respectively. Apoptosis of MG-63 cells mediated by paclitaxel was dependent on treatment duration. Interestingly, in cells treated with pirarubicin, apoptosis was related to treatment duration at concentrations of 10²–10³ nM, whereas the effect of treatment duration was less marked at concentrations >10⁴–10⁵ nM. Furthermore, paclitaxel and pirarubicin suppressed the expression of PCNA, cyclin D1, cyclin E and Bcl-2, and increased Bax expression. Conclusion: These results suggest that the G2/M or G0/G1 cell cycle arrest and apoptosis induced by paclitaxel and pirarubicin are Bcl-2/Bax dependent, suggesting favorable effects of combination therapy with paclitaxel and pirarubicin in the treatment of osteosarcoma.

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

“…These results suggest that THP partially overcomes the resistance caused by overexpression of P-gp and that THP may play an important role in treatment of patients with refractory or recurrent high-grade osteosarcoma. In fact, THP has also shown favorable activity in various types of cancer cells, including P-gp overexpressing breast cancer [27] , ADM-resistant lymphoblastoma [28] , MG-63 cells [29] and bladder cancers [30] in vitro, and has substantial clinical activity against various tumors without severe side effects [4][5][6][7]15,16] . Despite the ability of THP to overcome MDR in clinical studies [6,16,17] , very little is known about THP-induced cytotoxicity and the underlying mechanisms of pirarubicin on MDR osteosarcoma cells.…”

Anticancer Effects of Imperatorin Isolated from Angelica dahurica: Induction of Apoptosis in HepG2 Cells through both Death-Receptor- and Mitochondria-Mediated Pathways

“…The two compounds have different modes of action and toxicity, except for a common higher occurrence of myelosuppression and nausea/vomiting [31,32]. The combination of cisplatin and etoposide (PE) in the treatment of MBC as first-line therapy was investigated in four studies and showed an RR ranging from 24 to 63% (table 2) [33,34,35,36]. Major toxicities included neutropenia, thrombocytopenia and nausea/vomiting.…”

DNMT Inhibitors and HDAC Inhibitors Regulate E-Cadherin and Bcl-2 Expression in Endometrial Carcinoma in vitro and in vivo

“…Downregulation of Bcl-2 mRNA in leukemic patients using antisense technology resulted in increased apoptosis and potentiation of the effect of antineoplastic drugs in these patients [20]. Cell cycle arrest in G2/M or G0/G1 has been attributed to Bcl-2 [21]. However, Bcl-2 regulation has not been well studied in EC.…”