Silibinin a potent agent in lung cancer control

Lung cancer, the leading cause of cancer-related deaths worldwide, is a disease characterized by uncontrolled cell growth and proliferation in the lung, and the prognosis remains poor with 5-year survival rate of only 10–15%. Studies demonstrate that exposure to cigarette smoke and other environmental pollutants increased cytokine and chemokine secretion by macrophagesare and led to lung tumorigenesis with pulmonary morbidity and mortality.

Silibinin
     Since angiogenic potential of tumors can be enhanced by macrophages via STAT3 activation and thus lead to migration and/or proliferation of tumor cells. The agents targeting cytokine/growth factor induced signaling pathways involved in angiogenesis may be effective in lung cancer control.
     Silibinin is a flavonoid isolated from milk thistle seeds and has also demonstrated anti-cancer effects against a variety of cancers, such as human prostate adenocarcinoma, nonsmall human lung carcinoma and human colon cancer. In mechanistic studies, silibinin is found to produce the effects by inhibiting angiogenesis, macrophage accumulation, and cyclooxygenase 2 (COX2) and inducing nitric oxide synthase (iNOS).

     In the newest paper, Tyagi et al. reported their study on the subject. They found that multiple signaling pathways could be regulated by cytokine mixture treatment in LM2 Cells. JAK and MEK inhibitors, AG-490 and PD98059, reduced cytokine mixture-induced STAT3 and STAT1 activation and thus blocked COX2 and iNOS expression, while EGFR and NF-kB Inhibitors also showed the same effects on STAT3, STAT1, COX2, and iNOS in LM2 Cells. Treatment of silibinin significantly decreased both cell viability and proliferation in LM2 Cells. The mechanism studies showed that just like the pathway inhibitors above, silibinin exhibit negative effects on cytokine mixture-induced STAT3, STAT1, Erk1/2, and NF-kB ctivation in LM2 cells[1].
     Taken together, silibinin can blocked COX2 and iNOS expression in LM2 cells by regulating multiple signaling pathways.Therefore, silibinin may represent a novel agent in lung cancer control. In the newest paper published on Cancer Research, Xin et al. reported their study on effects of AZD1480 on tumor  BSI-201 and metastasis. The data in Renca tumor model showed that AZD1480 inhibited tumor growth in vivo with a reduction in tumor myeloid cell infiltration, as well as tumor angiogenesis. On an experimental lung metastasis model, AZD1480 was indicated to inhibit lung metastasis and factors important for pre-metastatic niche formation. Moreover, AZD1480 was confirmed to modulates the metastatic environment. On a human renal cell carcinoma xenograft, AZD1480 also presented the anti-angiogenic and anti-metastatic effects[2].
     In summary, these results showed that the antiangiogenic effects of AZD1480 may be mediated by blocking JAK/STAT3 in tumor cells. Thus, blocking JAK/STAT3 activity with AZD1480 may be effective in the treatment of solid malignancies by inhibiting tumor growth and preventing invasion and metastasis.