Yu Richard Ming Chuan, Selvarajah Gayathri Thevi, Tan Geok Chin, Cheah Yoke-Kqueen
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Int J Breast Cancer. 2022 Jul 21;2022:7168210. doi: 10.1155/2022/7168210. eCollection 2022.
Gold-based anticancer compounds have been attracting increasing research interest due to their ability to kill cancer cells resistant to platinum-based compounds. Gold I- and gold III-based complexes have shown satisfactory anticancer activities. In this study, two new fluorine-incorporated gold (I) compounds such as PhPAu[SC(OMe)=NCHF-3] and DPPFeAu[(SC(OMe)=NCHF-3)] were evaluated for their activities against human breast cancer cell lines, primary breast cancer cells, and breast cancer stem cells (parental breast cancer stem cells, BCSC-P, and breast cancer stem cells, BCSC). Assays for growth inhibition and cytotoxicity, including real-time cell analysis, were carried out to screen effective antibreast cancer compounds. In addition, further assays such as apoptosis, caspase 3/7 activity, and cell cycle analysis were performed to observe the action and mechanism of killing breast cancer cells by the selected gold I compound, PhPAu[SC(OMe)=NCHF-3]. The gold (I) compound, PhPAu[SC(OMe)=NCHF-3], showed low toxicity to H9c2 normal cells and significant growth inhibition in MDA-MB-231 and MCF-7 cells, primary breast cancer cells, and breast cancer stem cells (BCSC-P and BCSC). The IC doses of the gold (I) compound PhPAu[SC(OMe)=NCHF-3] against the breast cancer cell lines MDA-MB-231 and MCF-7 were approximately 6-fold lower than that of cisplatin (cis-diamineplatinum (II) dichloride, CDDP). Moreover, the compound PhPAu[SC(OMe)=NCHF-3] induced caspase 3/7-dependent apoptosis and cell cycle arrest at S and G2/M phases. PhPAu[SC(OMe)=NCHF-3], a gold (I) compound incorporated with fluorine, is a potential candidate for the treatment of breast cancer.
由于金基抗癌化合物能够杀死对铂基化合物耐药的癌细胞，它们已引起越来越多的研究兴趣。基于金（I）和金（III）的配合物已显示出令人满意的抗癌活性。在本研究中，评估了两种新的含氟金（I）化合物，如PhPAu[SC(OMe)=NCHF-3]和DPPFeAu[(SC(OMe)=NCHF-3)]对人乳腺癌细胞系、原发性乳腺癌细胞和乳腺癌干细胞（亲代乳腺癌干细胞，BCSC-P，以及乳腺癌干细胞，BCSC）的活性。进行了包括实时细胞分析在内的生长抑制和细胞毒性测定，以筛选有效的抗乳腺癌化合物。此外，还进行了进一步的测定，如凋亡、半胱天冬酶3/7活性和细胞周期分析，以观察所选金（I）化合物PhPAu[SC(OMe)=NCHF-3]杀死乳腺癌细胞的作用和机制。金（I）化合物PhPAu[SC(OMe)=NCHF-3]对H9c2正常细胞毒性低，对MDA-MB-231和MCF-7细胞、原发性乳腺癌细胞以及乳腺癌干细胞（BCSC-P和BCSC）有显著的生长抑制作用。金（I）化合物PhPAu[SC(OMe)=NCHF-3]对乳腺癌细胞系MDA-MB-231和MCF-7的半数抑制浓度（IC）比顺铂（顺二氯二氨合铂（II），CDDP）低约6倍。此外，化合物PhPAu[SC(OMe)=NCHF-3]诱导半胱天冬酶3/7依赖性凋亡，并使细胞周期停滞在S期和G2/M期。含氟金（I）化合物PhPAu[SC(OMe)=NCHF-3]是治疗乳腺癌的潜在候选药物。
