Abstract
BackgroundTubeimoside-I (TBM), a plant-derived bioactive compound, shows antitumor activity in different tumors and can enhance the efficacy of chemotherapeutic agents. However, the detail mechanism underlying remains to be elucidated.MethodsThe cytotoxic potential of TBM towards CRC cells was examined by CCK8 assay, colony formation, LDH release assay, flow cytometry method and Western blots. The ROS levels, autophagy, apoptosis, chemosensitivity to 5-FU or DOX, etc. were determined between control and TBM-treated CRC cells.ResultsIn this study, we found that TBM could inhibit proliferation and induce apoptosis in colorectal cancer (CRC) cells. Intriguingly, TBM treatment could either promote autophagy initiation by ROS-induced AMPK activation, or block autophagy flux through inhibiting lysosomal hydrolytic enzymes, which leaded to massive impaired autophagylysosomes accumulation. Administration of autophagy initiation inhibitor (3-MA or selective ablation of autophagy related proteins) relieves TBM-induced CRC suppression, while combination use of autophagy flux inhibitor chloroquine (CQ) slightly augments TBM-induced cell death, suggesting that impaired autophagylysosomes accumulation contributes to TBM-induced growth inhibition in CRC cells. Notably, as an autophagy flux inhibitor, TBM works synergistically with 5-fluorouracil (5-FU) or doxorubicin (DOX) in CRC suppression.ConclusionTogether, our study provides new insights regarding the anti-tumor activity of TBM against CRC, and established potential applications of TBM for CRC combination therapies in clinic.
Highlights
Tubeimoside-I (TBM), a plant-derived bioactive compound, shows antitumor activity in different tumors and can enhance the efficacy of chemotherapeutic agents
To further verify its anti-colorectal cancer (CRC) activity, lactate dehydrogenase (LDH) release assay was performed and the results showed that TBM treatment exhibited marked cytotoxicity in SW480 and HCT116 cells (Fig. 1c)
Coadministration of 3MA, a class III PI3K inhibitor, with TBM failed to Reactive oxygen species (ROS)/Adenosine monophosphate-activated protein kinase (AMPK) axis contributes to TBM-induced autophagy initiation Previous studies have shown that TBM promote cell death mainly by triggering a mitochondrial-related apoptotic pathway [13], which may decrease the production of energy and activate AMPK signaling pathway to initiate autophagy
Summary
Tubeimoside-I (TBM), a plant-derived bioactive compound, shows antitumor activity in different tumors and can enhance the efficacy of chemotherapeutic agents. 1.8 million new colorectal cancer cases and 881,000 deaths in 2018 [1, 2]. Development of new drugs for colorectal cancer is an urgent need. Tubeimoside-I (TBM), a triterpenoid saponin, is isolated from Rhizoma Bolbostemmatis and shows antitumor activity in different tumor such as promyelocytic leukemia, lung cancer, cervical cancer, nasopharyngeal carcinoma, esophageal carcinoma with low toxicity [6, 7]. Tubeimosides are effective in combination therapies, at targeting drug-resistant cancerous cells [13]. The underlying mechanisms of its anti-tumor activity have not been fully clarified so far, especially in CRC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Experimental & Clinical Cancer Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
