Abstract 5982: Cannabinoid derived product is a potential novel therapeutic for papillary thyroid carcinoma

Abstract

Abstract Papillary thyroid carcinoma (PTC) is the most common thyroid cancer that usually affects women ages 20-50, presenting as an asymptomatic neck mass. Total or partial thyroidectomy shows an excellent prognosis; however, investigation into non-invasive therapeutics with minimal adverse effects is ongoing. In addition to driver mutations such as BRAF, RAS, and RET-PTC, p53 mutations have also been identified. The loss of function of p53 is linked to cancer progression from PTC to poorly differentiated thyroid cancer and possibly anaplastic thyroid cancer. The disruption of the Wnt cell pathway is documented to be related to malignant cell transformation in thyroid cancer, leading to remarkable upregulation of c-myc, resulting in enhancement of tumor growth and drug resistance. Previous studies revealed that upregulation of BCL-2 occurs at later stages of tumorigenesis and is involved in chemotherapy resistance in some forms of cancer. In PTC, the downregulation of BCL-2 is linked to its favorable prognosis. Cannabinoid Derived Products (CDPs) have shown effectiveness in inhibiting different types of cancer, with research dating back to the 1970s. Ongoing in-vitro and in-vivo studies show that CDPs can effectively modulate tumor growth. However, the apoptotic properties of CDPs are largely dependent on the cancer type and drug dose/concentration. Our investigation focuses on CDPs and its potential anti-cancer effects by modulation of gene expression. We investigated its effects on gene expression of p53, c-Myc, and BCL-2 in K1 cell line which consists of PTC cells obtained from metastasis of well-differentiated PTC. K1 PTC cells (1 x106 cells/mL) were cultured with CDPs and incubated at 37°C under 5% CO2 for 24 and 48 hours. Cells were harvested, and cell viability was determined via trypan blue exclusion assay. Using qRT-PCR, we determined the effects of CDPs on the expression of TP53, c-Myc, and BCL-2. Results show that the CDPs decreased the viability (p< 0.001) of K1 PTC cells in a dose and time-dependent manner. Within 24 hours, the cannabinoid-containing product increased the gene expression of TP53 (p < 0.01) and decreased the gene expression of BCL-2 (p< 0.01) and c-Myc (p< 0.05) in K1 PTC cells. The results suggest that CDPs interact as a potential regulator in cancer with the upregulation of p53 and downregulation of BCL-2 and c-Myc. Further in-vitro and in-vivo studies are needed to understand the mechanism and therapeutic potential of cannabinoid-containing products in papillary thyroid cancer. Citation Format: Carolina Taico, Ibrahim Musa, Fariba Ardalani, Anish Maskey, Nan Yang, Joseph Breslin, Raj Tiwari, Jan Geliebter, Xiu Min Li. Cannabinoid derived product is a potential novel therapeutic for papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5982.