Thyroid cancers, the most common endocrine malignancies, are known to develop as either benign or malignant and to present a rapidly growing incidence in recent years. Based on pathological characteristics thyroid cancer can be classified into three classes, papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), and anaplastic thyroid cancer (ATC) 1. Among these three TCs, the ATC is known as undifferentiated with high aggressiveness and invasiveness properties. Indeed, patients with ATC survive only four to six months after being diagnosed 2.
While surgery remains the mainstay of the treatment of TC, combination therapeutic approaches including hyper-fractionated accelerated external beam radiotherapy, followed by combination of chemotherapies with or without palliative care have been suggested as first-line treatments of ATC patients 3. Due to the failure of single-drug chemotherapy, a combination of two or more agents such as Cisplatin, Docetaxel, Doxorubicin, Paclitaxel, and Pegfilgrastim is administered to ATC patients. However, the second-line treatment comprises more targeted options such as anti-angiogenic drugs, tyrosine kinase inhibitors, and hyperactive BRAF, mTOR, and/or BCR-ABL targeted agonists and multi-kinase inhibitors 2,3.
Several dietary components are of particular interest as anti-cancer molecules, and the most common examples are curcumin, epigallocatechin-3-gallate (EGCG), genistein, and resveratrol 4. Allegri et al. (2018) evaluated the anticancer capacity of the aforementioned compounds against ATC and found curcumin to be the best anti-ATC agent 5. Curcumin, the main component of the spice turmeric (Curcuma longa), is a polyphenol molecule with numerous medicinal values. Curcumin is well known for its great and specific in vitro and in vivo anti-cancer aptitudes against cancer in breast, colon and rectum, head and neck, pancreas, prostate, and thyroid. However, despite the clear therapeutic benefits, curcumin has some limitations, such as low bioavailability and quick metabolism, which significantly reduced its clinical effectiveness 6.
Aiming to overcome the pharmacokinetics limitations and at the same time to utilize the native therapeutic effects of curcumin, countless efforts were paid on synthesizing curcumin analogues. Interestingly, compared to the native one, few analogues showed better activity, while others exhibited similar or less performance 7. PAC 8 is a novel curcumin analogue synthesized by Youseff et al. 9. Until now, the anticancer activity of PAC has been evaluated against breast cancer 10,11, colon cancer 12, and oral cancer 8. Importantly, PAC exhibited better anti-cancer activity, greater biodistribution, and longer bioavailability compared to curcumin 10,11.
Considering the aforementioned discussion, we aimed in the present study to evaluate the anti-cancer capacity of PAC against ATC both in vitro and in vivo.