{Reference Type}: Journal Article
{Title}: Inactivation of TFEB and NF-κB by marchantin M alleviates the chemotherapy-driven pro-tumorigenic senescent secretion.
{Author}: Niu H;Qian L;Sun B;Liu W;Wang F;Wang Q;Ji X;Luo Y;Nesa EU;Lou H;Yuan H;
{Journal}: Acta Pharm Sin B
{Volume}: 9
{Issue}: 5
{Year}: Sep 2019
{Factor}: 14.903
{DOI}: 10.1016/j.apsb.2019.08.007
{Abstract}: It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-κB (NF-κB) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.