IMR Press / FBL / Volume 24 / Issue 2 / DOI: 10.2741/4719

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Nobiletin sensitizes colorectal cancer cells to oxaliplatin by PI3K/Akt/MTOR pathway
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1 The Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China
2 The Department of Oncology, Jing’an District Central Hospital of Shanghai, Fudan University, Shanghai, 200040, China
Front. Biosci. (Landmark Ed) 2019, 24(2), 303–312; https://doi.org/10.2741/4719
Published: 1 January 2019
(This article belongs to the Special Issue Leader sequences of coronavirus are altered during infection)
Abstract

Oxaliplatin is one of the most common chemotherapy drugs for colorectal cancer (CRC), but its application is greatly limited owing to the drug resistance. Nobiletin is a natural flavonoid isolated from citrus peel and has many biological functions, including anti-inflammatory, antitumor and neuroprotective activities. However, little is known about the effect of nobiletin on the anti-tumor activities of other chemotherapy drugs. In this study, we examined the effect of nobiletin on the efficacy of oxaliplatin in treatment of CRC by using two CRC cell lines. In vitro experiments indicated that nobiletin enhanced the inhibitory effect of oxaliplatin on the proliferation of CRC cells. Meanwhile, nobiletin promoted oxaliplatin-induced apoptosis of CRC cells, as demonstrated by the increased expression of pro-apoptotic proteins (Bax and cleaved-caspse3) and the down-regulation of anti-apoptotic protein Bcl-2. Mechanically, nobiletin sensitized CRC to oxaliplatin chemotherapy by down-regulating the PI3K/Akt/mTOR pathway. Taken together, our study has demonstrated that nobiletin could enhance the sensitivity of CRC to oxaliplatin chemotherapy, and provided a molecular basis for nobiletin’s potential applications in the chemosensitization of CRC.

Keywords
Colorectal cancer
Nobiletin
Oxaliplatin
Chemosensitization
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