Abstract
5-Fluorouracil (5-FU) regimen remains the backbone of the first-line agent to treat colon cancer, but often these patients develop resistance. Cancer stem cells (CSC’s) are considered as one of the key contributors in the development of drug resistance and tumor recurrence. We aimed to provide preclinical evidence for Antrodia cinnamomea (AC), as a potential in suppressing colon cancer CSC’s to overcome 5-FU drug-resistant. In-vitro assays including cell viability, colony formation, AC + 5-FU drug combination index and tumor sphere generation were applied to determine the inhibitory effect of AC. Mouse xenograft models also incorporated to evaluate in vivo effect of AC. AC treatment significantly inhibited the proliferation, colony formation and tumor sphere generation. AC also inhibited the expression of oncogenic markers (NF-κB, and C-myc), EMT/metastasis markers (vimentin and MMP3) and stemness associated markers (β-catenin, SOX-2 and Nanog). Sequential treatment of AC and 5-FU synergized and reduces colon cancer viability both in vivo and in vitro. Mechanistically, AC mediated anti-tumor effect was associated with an increased level of tumor suppressor microRNAs especially, miR142-3p. AC can be a potent synergistic adjuvant, down-regulates cancer stemness genes and enhances the antitumor ability of 5-FU by stimulating apoptosis-associated genes, suppressing inflammation and metastasis genes through miR142-3p in colon cancer.
Highlights
The prevalence of colorectal cancer (CRC) is expected to be higher than almost 2.2 million, it is expected that by 2030, the new cases and mortality would be around 1.1 million globally [1]
Recent studies have been associated with Cancer stem cells (CSC’s), which are a small group of cancer cells having the potential to undergo for self-renewal, differentiation and tumor initiation abilities [5]
Anti-cancer effect of Antrodia cinnamomea (AC) on colon cancer cells were determined by the cellular viability and colony formation assay by Sulforhodamine B (SRB) test
Summary
The prevalence of colorectal cancer (CRC) is expected to be higher than almost 2.2 million, it is expected that by 2030, the new cases and mortality would be around 1.1 million globally [1]. Of these patients have tumor relapse even after resection and is found to be related with the higher risk of cancer-associated death [2,3]. Most of these recrudescences arise during the period of the first. The drug resistance in colon cancer still remains a leading hindrance to successful chemotherapy. CSC’s are thought to be the key player involved in the failure of cancer therapy due to their substantial chemo-resistance properties that eventually leads to disease recurrence and metastasis [6]. More reports have surfaced to indicate for improving the cancer patient’s outcomes, traditional therapies approaches should be shifted to targeting the specific CSC’s [2].
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