Isoalantolactone Enhances the Antitumor Activity of Doxorubicin by Inducing Reactive Oxygen Species and DNA Damage

Abstract

Colon cancer is one of the most common cancer in the world. Doxorubicin (DOX) is a classical anti-tumor drug which widely used in treatment of cancers, however, high toxicity limited its further clinical application. Thus, it is urgent to find new drugs with low toxicity and high efficiency to treat colon cancer. Isoalantolactone (IATL), an isomeric sesquiterpene lactone isolated from the plant of inula helenium, has been reported to have anti-cancer activity against a variety of cancer cells. However, the function of IATL in colon cancer remains unclear. Here, we demonstrated that IATL inhibited colon cancer cell growth by increasing cellular reactive oxygen species (ROS) production. Further study showed that ROS accumulation contributed to DNA damage and JNK signaling pathway activation. In addition, we found that IATL markedly enhanced DOX-induced cell cytotoxicity in colon cancer cells. IATL in combination with DOX significantly increased the ROS production, induced DNA damage and activated JNK signaling pathway. Taken together, our data suggested that combined treatment with IATL and DOX may serve as a potential therapeutics for colon cancer.

Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells

“…Small molecules derived from natural products can exhibit various pharmacological properties, including anticancer activities [33]. Although isoalantolactone exhibits anticancer activities in several types of cancer cells [34][35][36][37], including imatinib-resistant chronic myeloid leukemia [38], its anticancer effect in the cisplatin-resistant model and whether it can regulate cancer metabolism remain largely unknown. In particular, cisplatin resistance remains a significant challenge in OC treatment, necessitating the exploration of novel therapeutic approaches [39,40].…”