Bleomycin A5 (hydrochloride) (Synonyms: Pingyangmycin)

Bleomycin A5 is an anticancer chemotherapeutic that binds DNA and induces DNA cleavage and strand breaks, it is highly toxic. Additionally, this compound induces apoptosis, alters cell cycle regulation, inhibits proliferation, and decreases tumor size in cellular and animal models of hemangioma. Bleomycin may also inhibit thioredoxin reductase.

In vitro: The IC50 of BLM alone to the cells was about 2.63 μg/ml. The IC50 of BLM was decreased to 1/3.8 and 1/9.5 of 2.63 μg/ml when used in combination with 2.63 μg/ml and 5 μg/ml W-131 [1]. Bleomycin A5 induced the activation of a JNK pathway in a dose-dependent manner. After 24h treatment, Bleomycin A5 induced dramatic cell death. DAPI nuclear staining assay revealed that PD98059 (10 μM) markedly enhanced bleomycin A5-induced apoptosis [2].

In vivo: In the rats, Bleomycin A5 induced pulmonary inflammation and fibrosis, increased the levels of malondialdehyde and tumour necrosis factor-α and enhanced accumulation of collagen in the lungs. Rolipram administration significantly attenuated these effects [3].

Clinical Trials: Bleomycin is clinically used to treat lymphomas, squamous cell carcinomas, and testicular cancer.

References:
[1].  Zhang H Q, He N G, Xue S B. Effect of bleomycin A5 with calmodulin inhibitor on the proliferation of S-180 cells in vitro[J]. Zhongguo yao li xue bao= Acta pharmacologica Sinica, 1990, 11(5): 470-473.
[2].  Yang L C, Yang S H, Tai K W, et al. MEK inhibition enhances bleomycin A5‐induced apoptosis in an oral cancer cell line: signaling mechanisms and therapeutic opportunities[J]. Journal of oral pathology & medicine, 2004, 33(1): 37-45.
[3].  Pan J B, Hou Y H, Zhang G J. Rolipram attenuates bleomycin A5‐induced pulmonary fibrosis in rats[J]. Respirology, 2009, 14(7): 975-982.