Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, Utah, USA.
Cancer Rep (Hoboken). 2023 Apr;6(4):e1790. doi: 10.1002/cnr2.1790. Epub 2023 Feb 11.
Prostate cancer (PC) is estimated to cause 13.1% of all new cancer cases in the United States in 2021. Natural bioactive compounds have drawn the interest of researchers worldwide in their efforts to find novel treatments for PC. Many of these bioactive compounds have been identified from traditional Chinese medicine (TCM) remedies often containing multiple bioactive compounds. However, in vitro studies frequently focus on the compounds in isolation.
We used mixture design response surface methodology (MDRSM) to assess changes in PC cell viability after 48 h of treatment to identify the optimal mixture of all 35 three-compound combinations of seven bioactive compounds from TCM.
We used berberine, wogonin, shikonin, curcumin, triptolide, emodin, and silybin to treat PC3 and LNCaP human PC cells at their IC50 concentrations that we calculated. These compounds modulate many chemotherapeutic pathways including intrinsic and extrinsic apoptosis, increasing reactive oxygen species, decreasing metastatic pathways, inhibiting cell cycle progression. We hypothesize that because these compounds bind to unique molecular targets to activate different chemotherapeutic pathways, they will act synergistically to decrease tumor cell viability. Results from MDRSM showed that two-way combinations were more effective than three-way or single compounds. Most notably wogonin, silybin, emodin and berberine responded well in two-compound combinations with each other in PC3 and LNCaP cells. We then conducted cell viability tests combining two bioactive compound ratios with docetaxel (Doc) and found significant results within the LNCaP cell line. In particular, mixtures of berberine and wogonin, berberine and silybin, emodin and berberine, and emodin and silybin reduced LNCaP cell viability up to an average of 90.02%. The two-compound combinations were significantly better than docetaxel treatment of LNCaP cells.
Within the PC3 cells, we show that a combination of berberine, wogonin and docetaxel is just as effective as docetaxel alone. Thus, we provide new combination treatments that are highly effective in vitro for treating androgen-dependent and androgen-independent PC.
前列腺癌（PC）预计将导致 2021 年美国所有新发癌症病例的 13.1%。天然生物活性化合物引起了全世界研究人员的兴趣，他们致力于寻找治疗 PC 的新方法。这些生物活性化合物中的许多已从传统中药（TCM）疗法中得到鉴定，这些疗法通常含有多种生物活性化合物。然而，体外研究经常集中在单独的化合物上。
我们使用混合物设计响应面法（MDRSM）来评估 PC 细胞活力在 48 小时治疗后的变化，以确定来自 TCM 的七种生物活性化合物的 35 种三化合物组合的最佳混合物。
我们使用小檗碱、白杨素、紫草素、姜黄素、雷公藤甲素、大黄素和水飞蓟宾在我们计算的 IC50 浓度下治疗 PC3 和 LNCaP 人 PC 细胞。这些化合物调节许多化疗途径，包括内在和外在凋亡，增加活性氧物种，减少转移途径，抑制细胞周期进程。我们假设，由于这些化合物与独特的分子靶标结合以激活不同的化疗途径，它们将协同作用以降低肿瘤细胞活力。MDRSM 的结果表明，双组合比三组合或单化合物更有效。最值得注意的是，在 PC3 和 LNCaP 细胞中，白杨素、水飞蓟宾、大黄素和小檗碱在相互作用的双化合物组合中反应良好。然后，我们结合两种生物活性化合物与多西紫杉醇（Doc）进行细胞活力测试，发现 LNCaP 细胞系中有显著结果。特别是，小檗碱和白杨素、小檗碱和水飞蓟宾、大黄素和小檗碱以及大黄素和水飞蓟宾的混合物将 LNCaP 细胞活力降低至平均 90.02%。双化合物组合明显优于多西紫杉醇治疗 LNCaP 细胞。
在 PC3 细胞中，我们表明小檗碱、白杨素和多西紫杉醇的组合与单独使用多西紫杉醇一样有效。因此，我们提供了在体外治疗雄激素依赖性和雄激素非依赖性 PC 方面非常有效的新联合治疗方法。
