Breast cancer (BC), the second most common cause of cancer-related deaths, remains a significant threat to the health and wellness of women worldwide. Even with new treatment options like chemotherapy and surgery, breast cancer’s lethality is still concerning. Natural compounds are considered to be a better therapeutic option for breast carcinoma because they are anticipated to have less side effects and to be more selective in targeting important proteins linked to the aberrant activation of pathways in breast cancer. A new indoloquinoline alkaloid found in the roots of the Periplocaceae family plant Cryptolepis sanguinolenta (Lindl.) Schltr known as cryptolepine has been shown to have the anticancer activity but this compound is poorly explored in breast cancer. However, little is known about the molecular processes via which this material functions in breast cancer. Earlier we have shown that Cryptolepine targets TOP2A which is highly overexpressed in breast cancer tissues and its overexpression correlates with worse overall survival and relapse-free survival in breast cancer patients. Consequently, our objective in this study was to investigate the molecular mechanism that Cryptolepine’s employs to inhibit breast carcinoma. We used the in-vitro and computational studies to look at the mechanism of action of cryptolepine in breast cancer. The results showed that the drug activated the P53 signalling pathway, which led to apoptosis and cell cycle arrest in breast cancer cells. Therefore, targeting P53, TOP2A in combination with other therapeutic agents will significantly enhance the response of BC patients to therapy and reduce the development of chemoresistance. This will help to reduce the burden on existing therapies, which are also currently ineffective due to a number of side effects and the emergence of drug resistance.
December 28, 2025