Abstract
Minocycline is a broad spectrum, semi-synthetic tetracycline analog that is used to treat bacterial infection. Recently, this drug has been receiving increasing attention for its non-antibiotic properties, including anti-inflammatory, tumor suppressive, and neuroprotective effects. Drosophila is a useful model organism for studying human metabolism and disease. In this study, we investigated the effects of minocycline on juvenile development and growth in Drosophila. Feeding minocycline to Drosophila larvae suppresses larval body growth and delays the timing of pupation in a dose-dependent manner. We found that the drug treatment decreased the activated form of Akt and S6K in peripheral tissues, which suggested that the insulin/target of rapamycin (TOR) signaling had been attenuated. Specifically enhancing TOR activity in the prothoracic gland (PG), the ecdysone-generating organ, attenuated the drug-induced developmental delay, which is consistent with the critical role of PG’s TOR signaling in determining pupation time. Our results reveal previously unrecognized effects of minocycline and offer a new potential therapeutic opportunity for various pathological conditions associated with insulin/TOR signaling.
Highlights
Minocycline (7-dimethylamino-6-desoxytertracycline) is a FDA approved, inexpensive antibiotic drug belonging to the second-generation tetracycline family
We found that minocycline treatment suppresses the insulin/target of rapamycin (TOR) signaling in larval tissues, which is shown by decreased levels of the activated forms of phospho-Akt and phospho-S6K
Since minocycline was first manufactured in the 1960s, it has long been used for a broad range of symptoms caused by bacterial infections, such as acne vulgaris
Summary
Minocycline (7-dimethylamino-6-desoxytertracycline) is a FDA approved, inexpensive antibiotic drug belonging to the second-generation tetracycline family. Numerous studies have recently highlighted the non-antibiotic properties of minocycline, such as anti-inflammatory and anti-apoptotic activities, as well as suppressive effects on cancer metastasis and angiogenesis[6,7,8,9] These characteristics support the potential use of the drug in the treatment of diseases, such as rheumatoid arthritis, inflammatory bowel syndromes, scleroderma, aortic aneurysms, and malignant tumors[6,10,11]. Enhancing TOR signaling in the prothoracic gland (PG), an endocrine organ that produces ecdysone steroid hormone, which dictates initiation of pupation, attenuates developmental delays induced by minocycline. This provides the underlying mechanism for minocycline effects on larval development
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