Tal Center for Integrative Medicine, Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.
Department of General Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Int J Oncol. 2015 Jan;46(1):308-16. doi: 10.3892/ijo.2014.2711. Epub 2014 Oct 17.
There is a need for new options for reducing the side effects of cancer treatment, without compromising efficacy, enabling patients to complete treatment regimens. The botanical compound LCS101 exhibits inhibitory effects on cancer cell growth, and reduces chemotherapy-induced hematological toxicities. The aim of the present study is to examine the selectivity of the effects of the compound, alone and in conjunction with conventional chemotherapy agents, on cancer cell proliferation. The effects of LCS101 were tested on a number of cancer cell lines (breast, MCF7, MDA-MB‑231; colorectal, HCT116; prostate, PC-3, DU-145) and on non-tumorigenic normal human epithelial cells (breast, MCF10A; prostate, EP#2). Cell viability was analyzed using an XTT assay and observed by light microscopy. Necrosis and apoptosis were examined using FACS analysis and immunoblotting. LCS101 selectively induced cell death in breast, colon and prostate cancer cell lines, as measured by XTT assay. Light microscopy and FACS analysis showed changes indicative of a necrotic process. LCS101 was also found to induce PARP-1 reduction in breast cancer cells, with no effect on non-tumorigenic breast epithelial cells. While LCS101 increased cell death in cancer cells exposed to doxorubicin and 5-FU, it showed a protective effect on non-tumorigenic human epithelial cells from chemotherapy-induced cell death. A similar selective effect was observed with apoptosis-associated PARP-1 cleavage. The findings demonstrate that the anti-proliferative effects exhibited by the botanical compound LCS101 are selective to cancer cells, and offer protection to non-tumorigenic normal epithelial cells from chemotherapy agents.
需要寻找新的选择来减少癌症治疗的副作用，同时又不影响疗效，使患者能够完成治疗方案。植物化合物 LCS101 对癌细胞生长具有抑制作用，并降低化疗引起的血液学毒性。本研究的目的是研究该化合物单独使用和与常规化疗药物联合使用对癌细胞增殖的选择性影响。在许多癌细胞系（乳腺 MCF7、MDA-MB-231；结肠 HCT116；前列腺 PC-3、DU-145）和非肿瘤性正常人类上皮细胞（乳腺 MCF10A；前列腺 EP#2）上测试了 LCS101 的作用。使用 XTT 测定法分析细胞活力，并通过光显微镜观察。使用 FACS 分析和免疫印迹检查坏死和细胞凋亡。LCS101 通过 XTT 测定法选择性地诱导乳腺癌、结肠癌和前列腺癌细胞系中的细胞死亡。光显微镜和 FACS 分析显示出与坏死过程相关的变化。LCS101 还诱导乳腺癌细胞中 PARP-1 的减少，而对非肿瘤性乳腺上皮细胞没有影响。虽然 LCS101 增加了暴露于阿霉素和 5-FU 的癌细胞的细胞死亡，但它对化疗引起的非肿瘤性人类上皮细胞的细胞死亡具有保护作用。与凋亡相关的 PARP-1 裂解也观察到类似的选择性效应。研究结果表明，植物化合物 LCS101 表现出的抗增殖作用对癌细胞具有选择性，并为非肿瘤性正常上皮细胞提供了对化疗药物的保护作用。
