Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of naturally occurring glucosinolate breakdown product Indole-3-Carbinol (I3C) as well as its abilities to induce selective cell death towards malignant cell. Therefore, the objective of the present study is to improve the therapeutic efficacy and prevention of doxorubicin (DOX)-induced toxicity, by the concurrent use of Indole-3-Carbinol (I3C). In this study, I3C was administered (20 mg/kg b.w., p.o.) to breast adenocarcinoma (Ehrlich ascites carcinoma) induced solid tumor bearing mice alone as well as in combination with DOX (5 mg/kg b.w., i.p.) in concomitant and pretreatment schedule. The results showed that concurrent administration of I3C and DOX significantly (P < 0.05) improved therapeutic efficacy as evidenced by reduction of tumor size and enhancement of host survivability. Oral administration of I3C significantly (P < 0.05) inhibited the expression of NF-κβ in both tumor cells and cardiac tissue as well as maximizes the therapeutic outcome in terms of tumor cell killing and toxicity. In addition, I3C sensitized tumor cells to DOX-therapy by down-regulating the expression of anti-apoptotic protein Bcl-2 and by up-regulating molecules like Bax, cytochrome c, caspases, which led to PARP cleavage and apoptosis. Significant inhibition of angiogenesis along with reduction in the serum levels of VEGF-A and MMP-9 further contribute to the sensitization accomplished by I3C. Moreover, we also found that I3C provided additional host survival advantages by attenuated DOX-induced toxicities through modulation of Nrf2/ARE pathway and promoted expression of cytoprotective proteins HO-1, NQO1 and GSTπ in cardiac tissue. In addition, I3C significantly attenuated DOX-induced inflammation by down-regulation of NF-kβ, iNOS, COX-2 and IL-6 in cardiac tissue. Thus, the present study clearly suggested therapeutic benefit of I3C in combination with DOX by augmenting anticancer efficacy and diminishing toxicity to the host.

各种流行病学和临床前研究已经确定了天然存在的芥子油苷分解产物Indole-3-Carbinol（I3C）的癌症化学预防潜力，以及其诱导针对恶性细胞的选择性细胞死亡的能力。因此，本研究的目的是通过同时使用吲哚-3-甲醇（I3C）来提高治疗效果并预防阿霉素（DOX）诱导的毒性。在这项研究中，将I3C（20 mg / kg bw，口服）给予乳腺腺癌（Ehrlich腹水癌）诱导的带有实体瘤的小鼠，以及与DOX（5 mg / kg bw，ip）联合使用并进行预处理日程。结果显示I3C和DOX的同时给药显着（P <0。05）肿瘤大小的减少和宿主存活率的提高证明了治疗效果的提高。口服I3C可以显着（P <0.05）抑制肿瘤细胞和心脏组织中NF-κβ的表达，并在杀死肿瘤细胞和毒性方面最大化治疗效果。此外，I3C通过下调抗凋亡蛋白Bcl-2的表达以及上调Bax，细胞色素c，胱天蛋白酶等分子来激活DOX疗法，从而导致PARP裂解和凋亡。血管生成的显着抑制以及血清VEGF-A和MMP-9的降低进一步促进了I3C的致敏作用。而且，我们还发现，I3C通过调节Nrf2 / ARE途径减弱DOX诱导的毒性并促进心脏组织中细胞保护蛋白HO-1，NQO1和GSTπ的表达，提供了其他宿主存活优势。此外，I3C通过下调心脏组织中的NF-kβ，iNOS，COX-2和IL-6来显着减轻DOX诱导的炎症。因此，本研究清楚地表明，I3C与DOX结合可通过增强抗癌功​​效和降低对宿主的毒性来治疗。