Sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the PI3K-Akt-mTOR signaling pathway.

Sodium cantharidate (SCA) is a derivative of cantharidin obtained by its reaction with alkali. Studies have shown that it inhibits the occurrence and progression of several cancers. However, therapeutic effects of SCA on breast cancer are less well studied. This study aimed to clarify the effect of SCA on breast cancer cells and its mechanism, and to provide a scientific basis for the clinical use of SCA for the treatment of breast cancer. The results of cell counting kit-8, colony formation assay, and 5-ethynyl-2'-deoxyuridine staining showed that SCA inhibited breast cancer cell proliferation. Wound-healing and transwell assays demonstrated that SCA inhibited the migration and invasion of breast cancer cells. Transmission electron microscopy revealed that SCA induced autophagy in breast cancer cells. RNA sequencing technology showed that SCA significantly regulated the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway, which was further verified using western blotting. The inducing effect of SCA on breast cancer autophagy was reversed by the mTOR activator MHY1485. In addition, subcutaneous xenograft experiments confirmed that SCA significantly inhibited tumor growth in vivo. Hematoxylin-eosin, TdT-mediated dUTP nick-end labeling, and immunohistochemical staining indicated that SCA induced tumor cell autophagy and apoptosis in nude mice without causing organ damage. In summary, we found that SCA promoted breast cancer cell apoptosis by inhibiting the PI3K-Akt-mTOR pathway and inducing autophagy.

WITHDRAWN: Anti-lung Cancer Mechanism of Hedyotis Diffusa Willd Based on Network Pharmacology and Molecular Docking

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Hedyotis diffusa injection induces ferroptosis via the Bax/Bcl2/VDAC2/3 axis in lung adenocarcinoma.

BACKGROUND: Lung cancer has the highest mortality rate among all cancer types. In combination with multiple chemotherapeutic options, traditional Chinese medicine has proven indispensable for the comprehensive treatment of lung cancer. PURPOSE: To investigate the effects of Hedyotis diffusa on lung adenocarcinoma cell lines and a BALB/c nude mouse xenograft model, and determine whether HDI could induce ferroptosis in lung adenocarcinoma cells along with the underlying mechanism. METHODS: The anti-tumor activity of HDI was determined in vitro by cell counting kit-8, clonogenic, and transwell assays. Subsequently, electron microscopy, a lipid reactive oxygen species assay, ferrous ion staining, and a malondialdehyde assay were performed to determine the effect on ferroptosis in lung adenocarcinoma cells. The mechanism was then further investigated using small molecule inhibitors, siRNA, and plasmid overexpression in vitro. Finally, the effects of HDI were assessed in tumor-bearing BALB/c nude mice, and HE staining was performed to observe tissue damage after HDI treatment. RESULTS: In vitro experiments showed that HDI could inhibit the viability of lung adenocarcinoma cells and induce lung adenocarcinoma cells ferroptosis via mechanisms independent of GPX4 and PUFA-PLS pathways but closely associated with VDAC2/3. HDI regulated VDAC2/3 activity by promoting Bax via inhibiting Bcl2, thereby inducing ferroptosis in lung adenocarcinoma cells. Furthermore, in vivo experiments showed that HDI significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice with less organ damage and toxicity, and significantly increased the expression of the ferroptosis-related indicators 4HNE, TFR, and HMOX1 in tumor tissue. CONCLUSION: HDI can significantly reduce the survival of lung adenocarcinoma cells in vitro, inhibit the growth of subcutaneously transplanted tumors in BALB/c nude mice in vivo, and induce ferroptosis in lung adenocarcinoma cells via Bcl2 inhibition to promote Bax regulation of VDAC2/3.