Cyclopamine tartrate, an inhibitor of Hedgehog signaling, strongly interferes with mitochondrial function and suppresses aerobic respiration in lung cancer cells

BMC Cancer
Md Maksudul AlamLi Zhang

Abstract

Aberrant Hedgehog (Hh) signaling is associated with the development of many cancers including prostate cancer, gastrointestinal cancer, lung cancer, pancreatic cancer, ovarian cancer, and basal cell carcinoma. The Hh signaling pathway has been one of the most intensely investigated targets for cancer therapy, and a number of compounds inhibiting Hh signaling are being tested clinically for treating many cancers. Lung cancer causes more deaths than the next three most common cancers (colon, breast, and prostate) combined. Cyclopamine was the first compound found to inhibit Hh signaling and has been invaluable for understanding the function of Hh signaling in development and cancer. To find novel strategies for combating lung cancer, we decided to characterize the effect of cyclopamine tartrate (CycT), an improved analogue of cyclopamine, on lung cancer cells and its mechanism of action. The effect of CycT on oxygen consumption and proliferation of non-small-cell lung cancer (NSCLC) cell lines was quantified by using an Oxygraph system and live cell counting, respectively. Apoptosis was detected by using Annexin V and Propidium Iodide staining. CycT's impact on ROS generation, mitochondrial membrane potential, and mitochondrial m...Continue Reading

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Citations

Nov 10, 2018·Cell & Bioscience·Sarada Preeta KalainayakanLi Zhang
Oct 15, 2019·Chemistry & Biodiversity·Chiyu SunXiaofeng Chen
Apr 23, 2020·International Journal of Oncology·Lu XiaLu-Zhe Sun
Jan 10, 2019·Therapeutic Advances in Medical Oncology·Nuozhou WangGeorge G Chen
Dec 12, 2019·Frontiers in Cell and Developmental Biology·Yoan ArribatFrancesca Amati
May 14, 2020·International Journal of Molecular Sciences·Poorva GhoshLi Zhang
Dec 21, 2016·Frontiers in Pharmacology·Zhijie XuZhicheng Gong

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Methods Mentioned

BETA
immunoprecipitation

Software Mentioned

R
Carestream

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