Solamargine Inhibits Prostate Cancer Cell Growth and Enhances the Therapeutic Efficacy of Docetaxel via Akt Signaling

Abstract

Prostate cancer (PCa) has become a leading cause of cancer-associated incidence and mortality in men worldwide. However, most primary PCas relapse to castration-resistant PCa (CRPC) after androgen deprivation treatment. The current treatment for CRPC is based on chemotherapeutic drugs such as docetaxel, while the development of chemoresistance and severe side effects limit the therapeutic benefit. Solamargine, a natural alkaloid isolated from a traditional Chinese herbal medicine known as Solanum nigrum, exhibits antitumor activity in various human cancers. In this study, we demonstrated that solamargine substantially inhibited CRPC cell growth in a dose-dependent manner through the suppression of phosphoinositide 3-kinase (PI3K)/Akt signaling. Moreover, solamargine exhibited significant antitumor effects in mouse xenograft models. Bioinformatics analysis of docetaxel-resistant PCa cells indicated that the PI3K/Akt pathway mediated the chemoresistance of CRPC. Furthermore, solamargine significantly enhanced the efficacy of docetaxel in PCa cells. These results reveal the therapeutic potential of solamargine against human PCa.

Chinese herbal medicines for prostate cancer therapy: From experimental research to clinical practice

“…These findings may provide therapeutic targets for CRPC. Solamargine enhanced the efficacy of docetaxel by inhibiting the PI3K/Akt pathway in CRPC cells ( Ge et al, 2022 ). Han et al (2020) screened the anti-prostate cancer components of TCM.…”

Active components of Solanum nigrum and their antitumor effects: a literature review

“…This leads to the suppression of CRPC cell growth through AMPKα-mediated inhibition of p65 ( 71 ). When combined with docetaxel, SM enhances the antitumor effect of docetaxel ( 72 ). According to Zhang et al., the treatment of human cholangiocarcinoma cells QBC939 with SM increases the expression of apoptosis-related proteins, inhibiting cell viability.…”

Anticancer activity of glycoalkaloids from Solanum plants: A review

“…have the potential to be used in therapy together with anticancer drugs (Ge et al, 2022). SM activates AMPKα, reducing the protein expression of MUC1 and NF-κB subunit p65 in vitro in castration-resistant PC CRPC cells and inhibiting tumor growth in vivo.…”

“…This signaling pathway seems to be responsible for the chemoresistance of this disease. Furthermore, it increases the anticancer effect caused by docetaxel; thus, it may have the potential to be used in therapy together with anticancer drugs ( Ge et al, 2022 ). SM activates AMPKα, reducing the protein expression of MUC1 and NF-κB subunit p65 in vitro in castration-resistant PC CRPC cells and inhibiting tumor growth in vivo .…”