Surfactin Ameliorated the Internalization and Inhibitory Performances of Bleomycin Family Compounds in Tumor Cells

Abstract

The cationic glycopeptide bleomycin (BLM) is a broad-spectrum chemotherapy drug clinically applied to treat various malignant tumors. The poor cell membrane permeability of BLM, which is prone to high dose usage and may consequently induce dose-dependent lung toxicity, is a sticking point to limit clinical applications of BLM. As a commercial biosurfactant, the anionic lipopeptide surfactin (SF) is well known for its potent ability to disturb membranes and widely applied in cosmetic area as a permeabilization synergist. In this work, our in vitro investigations showed that SF could ameliorate the cell internalization of BLM, and the combined usage of SF notably improved the antitumor activity of BLM or its analogues while having no obvious effects on normal cells. Subsequent in vivo assessments on the subcutaneous treatment of A375 melanoma in mice demonstrated that SF could also enhance the therapeutic effects of BLM family compounds in subeffective doses, with no obvious toxicities on lungs and skin. Also, our preliminary results suggested the formation of complex micelles at the nanoscale by the self-assembly of BLM and SF, which may contribute to the ameliorated internalization and the antitumor effect of BLM. Therefore, SF could be applied as a potential synergist for BLM to reduce its treatment dose while maintaining the therapeutic effect on treatment of skin carcinoma, which provides us an alternative way to minimize the side effects of clinical BLM and facilitate the development of new BLM-type drugs.

Genome mining of Streptomyces sp. CB00271 as a natural high‐producer of β‐rubromycin and the resulting discovery of β‐rubromycin acid

“…The in vitro antitumor activities of β‐RUB ( 1 ), γ‐RUB ( 2 ), RUB CA1 ( 3 ), and β‐RUB acid ( 7 ) were respectively evaluated against four different human cancer cell lines, including the nonsmall cell lung cancer cell line A549, the liver hepatocellular carcinoma HepG2, the cervical cancer cell line Hela, and the colon tumor cell line Caco‐2 (Xiong et al, 2020). During the assays, the distinct purple precipitate of β‐RUB ( 1 ) or γ‐RUB ( 2 ) was clearly observed in serum under high concentrations (data not shown), therefore the relative solubilities of four compounds in serum were first determined based on the quantitative HPLC analyses.…”

“…The antitumor activity of β‐RUB ( 1 ), γ‐RUB ( 2 ), RUB CA1 ( 3 ), and β‐RUB acid ( 7 ), as well as the positive control BLM‐sulfate, were respectively evaluated in four different human tumor cell lines (A549, HepG2, Caco‐2, and Hela) by the standard CCK‐8 assay (Xiong et al, 2020). Briefly, cells were seeded in 96‐well plates with 4 × 10 3 cells per well and stabilized for 24 h. Then cells were treated with a certain agent at different concentrations in 100 µl media per well.…”

A review on green nanoemulsions for cosmetic applications with special emphasis on microbial surfactants as impending emulsifying agents

“…In a recent study, surfactin was used to enhance the drug‐delivering capacity of bleomycin (BLM). The addition of surfactin is reported to have enhanced the efficiency of receptor‐mediated endocytosis of BLM by destabilization of biological membranes, while keeping the resulting cytotoxicity of the formulation low, owing to the higher safety of surfactin in comparison with other surfactants (Xiong et al, 2020). Similarly, it was observed that almost 80% of surfactin‐treated wounds were closed, indicating that surfactin could also be used as an affordable wound healing drug (Yan et al, 2020).…”