Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada.
Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada.
Nutrients. 2024 Apr 24;16(9):1257. doi: 10.3390/nu16091257.
Prostate cancer, accounting for 375,304 deaths in 2020, is the second most prevalent cancer in men worldwide. While many treatments exist for prostate cancer, novel therapeutic agents with higher efficacy are needed to target aggressive and hormone-resistant forms of prostate cancer, while sparing healthy cells. Plant-derived chemotherapy drugs such as docetaxel and paclitaxel have been established to treat cancers including prostate cancer. Carnosic acid (CA), a phenolic diterpene found in the herb rosemary (Rosmarinus officinalis) has been shown to have anticancer properties but its effects in prostate cancer and its mechanisms of action have not been examined. CA dose-dependently inhibited PC-3 and LNCaP prostate cancer cell survival and proliferation (IC: 64, 21 µM, respectively). Furthermore, CA decreased phosphorylation/activation of Akt, mTOR, and p70 S6K. A notable increase in phosphorylation/activation of AMP-activated kinase (AMPK), acetyl-CoA carboxylase (ACC) and its upstream regulator sestrin-2 was seen with CA treatment. Our data indicate that CA inhibits AKT-mTORC1-p70S6K and activates Sestrin-2-AMPK signaling leading to a decrease in survival and proliferation. The use of inhibitors and small RNA interference (siRNA) approaches should be employed, in future studies, to elucidate the mechanisms involved in carnosic acid's inhibitory effects of prostate cancer.
前列腺癌是全球男性第二大常见癌症，2020 年导致 375304 人死亡。虽然有许多治疗前列腺癌的方法，但仍需要新型治疗药物来针对侵袭性和激素耐药性的前列腺癌，同时保护健康细胞。植物来源的化疗药物，如多西他赛和紫杉醇，已被确立用于治疗包括前列腺癌在内的癌症。迷迭香（Rosmarinus officinalis）中含有的酚类二萜类化合物 carnosic acid（CA）已被证明具有抗癌特性，但它在前列腺癌中的作用及其作用机制尚未得到研究。CA 呈剂量依赖性地抑制 PC-3 和 LNCaP 前列腺癌细胞的存活和增殖（IC：分别为 64、21µM）。此外，CA 降低了 Akt、mTOR 和 p70 S6K 的磷酸化/激活。CA 处理后，AMP 激活的蛋白激酶（AMPK）、乙酰辅酶 A 羧化酶（ACC）及其上游调节因子 sestrin-2 的磷酸化/激活显著增加。我们的数据表明，CA 通过抑制 AKT-mTORC1-p70S6K 和激活 sestrin-2-AMPK 信号通路，导致细胞存活和增殖减少。在未来的研究中，应使用抑制剂和小 RNA 干扰（siRNA）方法来阐明 CA 抑制前列腺癌的作用机制。
